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

Allele Receives Tissue Bank License for Manufacturing and Distribution of cGMP-compliant iPSCs

Allele Biotechnology & Pharmaceuticals has received a Tissue Bank License from the California Department of Public Health, making it the world’s first establishment to collect tissue for the manufacture and banking of induced pluripotent stem cells (iPSCs) for commercial applications.

Allele’s cGMP facility is dedicated to the generation, banking, and differentiation of iPSCs for therapeutic use and drug discovery. All tissues and cells are processed in a state-of-the-art cleanroom to satisfy FDA requirements for Phase III clinical trials and commercial production. The cleanroom’s modular space and adaptable design allow different areas to be dedicated to the manufacture of various iPSC-derived cells.

The first tissues were processed in August 2017 when the cGMP manufacturing suite officially opened after a 2-year construction and remodeling effort and nearly a decade of iPSC reprogramming research and optimization. The iPSCs generation process is fully cGMP- and GTP-compliant, beginning with the onsite collection of tissue from donors or clients by a physician. All cGMP manufacturing personnel have undergone extensive training with strict qualification and documentation measures to ensure successful reprogramming of cells in an ISO-5 environment. Once generated, iPSCs are banked and can be distributed or differentiated for transplantation into patients. The entire process is validated and performed under the umbrella of a 21 CFR-compliant quality system.

Generation of iPSCs is based on Allele’s proprietary mRNA-only protocol which was designed and optimized expressly for cGMP production. The methods were developed to produce iPSCs that are free from genomic integration of plasmid DNA, viruses, and feeder cells. According to CEO and the lead scientist behind the technology, Dr. Jiwu Wang, “The powerful mRNA technology developed by Allele’s researchers made it much easier for cells to enter clinical trials down the road and we expect multiple patent issuances shortly.”

The cGMP facility has a dedicated mRNA production area for the manufacture of cGMP-compliant mRNAs. In addition to supporting iPSC reprogramming efforts, cGMP mRNA will support ongoing internal development programs to generate iPSC derived cells. Current efforts are focused on the development of pancreatic beta cells, neurons, oligodendrocytes and their progenitor cells, hepatocytes, muscle cells, and mesenchymal cells.

Established in 1999, Allele Biotechnology has a mission to further therapeutic innovation by providing cutting edge technologies and clinical grade solutions to partners working in collaborative and creative ways to support preclinical studies and clinical trials in the stem cell therapy arena.

Roundtable on cGMP Stem Cell Manufacturing

Allele Biotechnology & Pharmaceuticals is hosting a cGMP Stem Cell Manufacturing Roundtable to discuss ways to accelerate stem cell-based therapies toward clinical development and commercialization. The roundtable will bring together top minds from academic settings, cGMP facilities, and biotech industries in an informal setting to explore partnerships and avenues for developing effective and marketable iPSC-derived therapies.

The meeting will be held on April 20th at The Hilton on Torrey Pines and will consist of four sessions covering (1) existing cGMP facilities, (2) manufacturing and quality systems, (3) regulatory concerns, and (4) business strategy.

Meeting highlights will be produced to summarize the presentations and discussions. For inquiries, contact info@allelebiotech.com or call 858-587-6645.

Allele-iPSC News Translate: iPS clinical research encounters a problem. Doctors say “the problem is not caused by iPSCs”

Kobe City Medical Center General Hospital and Riken Research Institute announced and reported to the Japanese government that a patient who had received allogeneic iPSC-derived cells developed an “epi retinal membrane”, which they subsequently removed by operation. Dr. Masayo Takahashi at Riken says “the problem is caused by the transplantation procedure, but not by iPSCs. This will not affect future clinical research that uses iPSCs.”

The laws that govern regenerative medicine in Japan mandates that the deaths and hospitalizations that occur during treatment need to be reported to the government as “serious harmful effects”. This is the first such report involving iPSC clinical research.

The problem occurred to a man in his 70s, who is at the risk of blindness due to “wet age-related macular degeneration”. Last June, he received a transplantation of the solution containing allogeneic iPSC-derived retinal pigment epithelium (RPE) in his left eyes. Last October, the epi retinal membrane and swelling started to develop and the membrane was removed on January 15.

The possibility exists that the solution leaked from the needle hole during the transplantation, and the leaked cells might have formed the membrane. The transplanted cells inside the retina are stable and there has been no decline in his eyesight.

Dr. Takahashi says “although this event qualifies as a serious harmful event, the patient’s condition has not worsened and there has been no rejection of transplanted cells”. Dr. Yasuo Kurimoto, a surgeon who performed the operation, says “the procedure was the problem. We would like to improve the method, in order to make iPSC therapy a common treatment.”

The current clinical trial targets patients with wet age-related macular degeneration and is run by the Kobe City Hospital, Riken, Osaka-University Hospital, and Kyoto-University CiRA (Dr. Shinya Yamanaka). Between last March and October, five patients have received the transplantation.

Original News Credits: https://www.kobe-np.co.jp/news/iryou/201801/0010902012.shtml

Tags: AMD, eye disease, iPSC, Japan iPSC, RPE, stem cells, Takanishi, Yamanaka

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