Allele Enters into Collaboration and Licensing Deal on its cGMP iPSC with Alpine BioTherapeutics for Vision Loss

SAN DIEGO--

June 12th, 2019 -- Allele Biotechnology and Pharmaceuticals, Inc. and Alpine BioTherapeutics Corporation entered into a research agreement for developing iPSC-derived cell therapy for treating retinal diseases. Both companies are based in San Diego, California.

iPSCs (induced pluripotent stem cells) have the potential to differentiate into all human tissue types and play an increasingly important role in regenerative medicine. Approximately a dozen clinical trials using iPSCs are currently underway around the globe.

Allele Biotechnology has been developing technologies to produce GMP grade human iPSCs and high-quality tissue-specific cells derived from them for 10 years. Allele’s core capabilities in this area include its proprietary and patented technologies utilizing mRNA for generation and differentiation of footprint-free iPSCs in its state-of-the-art commercialization-ready cGMP facility.

Alpine BioTherapeutics has developed a patented stem cell differentiation technique to robustly generate human retinal stem cells from pluripotent stem cells. Alpine’s cell therapy products will be used to treat blindness caused by Retinitis Pigmentosa, Stargardt disease, and dry AMD. The company claims their technique as by far the most efficient process known in the manufactured retinal cell category and is expected to yield the highest quality retinal cell for use in patients. This potentially translate into much lower variability and cost while also minimizing regulatory risk.

"This collaboration with Allele Biotechnology provides us a clear path forward for clinical use of our technology. There are only a handful of clinical grade iPSC lines available in the world and we are fortunate that we will now have access to one of the best. Moreover, the support of Allele’s cell scientists and cGMP experts will be of great advantage to enable us to move to IND and into clinical trials quickly”, said Dr. Jack J. Zhao, CEO of Alpine BioTherapeutics.

The agreement will provide Alpine BioTherapeutics priority access to Allele’s cGMP facility and will involve licensing one or more of Allele’s cGMP-grade human iPSC lines to generate cell therapy products for vision loss.

Dr. Jiwu Wang, Founder and CEO of Allele Biotechnology, said “We are excited that our technology synergizes with Alpine’s to make novel products with the potential to make a difference to millions of lives affected with debilitating eye disorders”

Allele and Addgene Partner to Increase Academic Access to the World’s Brightest Monomeric Fluorescent Protein

SAN DIEGO--(BUSINESS WIRE)--

April 23rd, 2019 -- Allele Biotechnology and Pharmaceuticals Inc., a San Diego based biotechnology company focused on the development and clinical translation of cutting-edge technologies, has partnered with Addgene, a global nonprofit organization helping scientists share plasmids, to further facilitate academic use of mNeonGreen. Addgene will leverage its field-leading distribution platform to increase the availability of mNeonGreen constructs to researchers around the world.

First reported in the journal Nature Methods in 2013 (Shaner et al.), mNeonGreen is the brightest monomeric fluorescent protein available on the market. Upon its release, Allele’s CEO Dr. Jiwu Wang stated, “mNeonGreen surpasses eGFP in every way, it’s brighter, more photostable, enables superresolution imaging, and is compatible with imaging equipment used for eGFP. It will replace eGFP as the fluorescent protein of standard.”

Since its release, mNeonGreen has been available exclusively at Allele Biotechnology, under a novel licensing model created by Allele specifically for academic users (Nature Methods: Technology Feature). According to Allele’s Marketing Director, Abbas Hussain, “Our licensing model was developed to simplify access to mNeonGreen constructs and create a close-knit community to share reagents and ideas of using the protein at far below market costs. We wanted to be a part of the conversation so we could develop new tools and closely assist our users. The model has been a huge success and we appreciate the enthusiastic support from the community.”

Over the years a number of new tools have emerged harnessing mNeonGreen, including species-specific and split versions of the protein and outstanding voltage and calcium. Allele has also developed a camelid derived VHH nanoantibody against mNeonGreen to enable various assays such as co-immunoprecipitation and secondary labeling. Many users further sub-cloned mNeonGreen into various plasmids or viral vectors, as different fusions, or under different promoters. These developments have spurred the discussions between Addgene and Allele to expand the mNeonGreen distribution to the academic community and allow mNeonGreen to truly establish itself as a fluorescent protein of standard.

Allele Biotechnology owns newly issued patents and pending applications on the mNeonGreen protein and antibodies against it, and is still the exclusive source for commercial licensing and opportunities related to mNeonGreen. Allele has funded external research and is continuously committed to developing novel tools that put to use the benefits of this brilliant fluorescent protein. Our current licensees could receive extra benefits from Allele such as nanoantibodies against mNeonGreen and continued technical support by Allele’s expert team.

Allele Biotechnology and SCM Lifescience Sign a Joint Research and Development Agreement to Develop iPSC-based Diabetes Treatment

SAN DIEGO--(BUSINESS WIRE)--

April 15th, 2019 -- San Diego-based Allele Biotechnology and Pharmaceuticals, Inc., officially announced a joint research and development agreement with South Korea’s SCM Lifescience Co., Ltd., for the development of diabetes therapies using pancreatic beta cells derived from induced pluripotent stem cells (iPSCs).

iPSCs can be derived from adult human tissue cells yet share the developmental potentials of embryonic stem cells. Currently Japan has 6 ongoing clinical trials utilizing this technology, but the rest of the world is now joining the movement with 4 clinical trials initiated outside of Japan in the past year.

Since 2009, Allele Biotechnology has been developing clinically compatible technologies to produce high quality iPSCs and tissue-specific cells from iPSCs. The pancreatic beta-cell program is powered by Allele’s core capabilities, including proprietary methods utilizing mRNA for generation and differentiation of iPSCs, and a state-of-art, commercialization-ready cGMP facility in San Diego, California.

Dr. Jiwu Wang, Founder and CEO of Allele Biotechnology, said, “We are excited to have a partnership with SCM Lifescience, which has years of experience in cell therapy clinical trials. This collaborative project will help us quickly generate first-in-human results in the fast-moving field of iPSC-based therapies.”

The purpose of the collaboration is to confirm the therapeutic applicability of Allele’s iPSC-derived pancreatic beta cells for diabetes and related indications. The initial efforts will be focused on developing an autologous product for certain forms of Type 3c Diabetes (T3cDM), that are inherently non-autoimmune in nature. Allele Biotechnology also envisages alternative, off-the-shelf allogeneic therapeutic products for other types of diabetes, taking advantage of its growing bank of cGMP-grade footprint-free iPSCs, and gene editing technologies.

SCM Lifescience currently has a number of allogeneic mesenchymal stem cell therapies in its pipeline, indications include chronic graft versus host disease, acute pancreatitis, severe atopic dermatitis, and liver cirrhosis. The new collaboration will expand its capabilities by exploring the iPSC-based market.

"We are pleased to collaborate with Allele Biotechnology for the development of diabetes treatment which will be a valuable addition to our current pipeline. Knowing Allele’s cGMP manufacturing experience, we are expecting a great synergy with our recent acquisition of CoImmune with its production site in North Carolina,” stated Dr. BG Rhee, CEO of SCM Lifescience.

New iPSC Lines Created for Clinical Development

iPSCs have been created using mRNA technologies, with cGMP control from donor screening, consenting, to skin punch, and throughout cell bank production.

SAN DIEGO, CA, USA, December 4, 2018 — After 3 years of cleanroom construction and 2 years of quality system establishment, Allele Biotech has produced its initial batch of 6 iPSC (induced pluripotent stem cells) lines that are ready for prime time.

Prior to Allele’s cGMP iPSC generation there were only ~3 GMP iPSC lines available for therapy development from other sources around the world, forcing several pluripotency inspired companies to resort to embryonic stem cells (ESCs) as their starting material. ESC lines have a number of limitations due to questions of whether they were created with consent that meets today’s standards, and whether there have been gaps in custody throughout their history of existence. As the stem cell-based therapy field ramps up towards its exponential phase, there are obvious reasons to produce additional functional cGMP iPS cell lines with diverse genetic backgrounds and differentiation potentials.

Allele’s iPSCs were created using its patented mRNA technologies, with full cGMP monitoring and documentation starting from donor consent, screening and tissue biopsy. In its San Diego facility that received California tissue bank license earlier this year, Allele’s highly trained and dedicated stem cell manufacturing team first produced dozens of banked fibroblast stocks that are fully cGMP-compliant. Now they are churning out iPSC lines at unprecedented pace. Even though it takes just 1-2 weeks to reprogram fibroblasts into iPSCs using the mRNA method, production of cGMP-compliant iPSCs takes 3-4 months due to the stringent testing and quality control assays Allele painstakingly developed and qualified.

In addition to iPSC generation and differentiation, Allele’s proprietary mRNA platform can be used to engineer human iPSCs in a one-time genetic modification event to generate a clonal iPSC line that can be developed into a master cell bank.

Allele has received notification that patents have been allowed in EU and Japan one month after receiving 2 US patents on generating mRNA-iPSCs. mRNA produced iPSCs are more stable and easier to differentiate as Allele has previously reported, and their manufacturing process is continually being improved and upgraded. Focusing on industrial use of iPSCs, Allele has established a suspension iPSC culture system that can generate billions of iPS cells in a closed system before induction to differentiation.

Allele Receives iPSC Patents Bolstering Current Production of Multiple Lines at Wholly Owned cGMP Facility

SAN DIEGO--(BUSINESS WIRE)--

October 31st, 2018 — Allele Biotechnology & Pharmaceuticals Inc. has received issuance notices from the U.S. Patent and Trademark Office for its first batch of patents covering the derivation of induced pluripotent stem cells (iPSCs). Allele’s proprietary technology uses only messenger RNA (mRNA) to reprogram human or other primate cells, avoiding many operational complications that other methods often encounter.

The patents were purposefully structured for the production of iPSCs using methods fully compliant with current good manufacturing practice (cGMP) regulations suitable even for phase III clinical trials and commercial production. Accordingly, the Allele team developed technologies to enable a feeder-free and genome integration-free reprogramming procedure with unparalleled efficiency and success rates.

“Companies in the iPSC industry, an industry still in its infancy, are able to access only 1 or 2 GMP-compatible lines and are often nervous about whether their highly valued differentiation protocols will work with these lines,” commented Dr. Jiwu Wang, CEO of Allele Biotech and a key inventor of these patents. “What we have put in motion starting this month is to continuously create fully cGMP-compliant iPSC lines. We intend to communicate with the FDA early and often to set high quality standards, which will enhance chances of success in the iPSC therapy field as a whole.”

Allele’s differentiation protocols also use mRNAs to direct cell fate. Because the costs of cGMP production are directly influenced by the time cells spend in culture, Allele’s efficient protocols will show a strong technical and economic advantage. Many academic labs and their spinoff companies have developed protocols to differentiate embryonic stem cells (ESCs) or iPSCs into a chosen lineage. Those protocols typically work well with just one ESC or iPSC line, whereas Allele’s protocols consistently work across all lines tested, ultimately enabling autologous cell therapies, which are widely considered to be the true power of the iPSC technology since its discovery by Dr. Shinya Yamanaka.

Operations are underway at Allele’s cGMP facility to produce dozens of iPSC lines. According to both industry and academic collaborators, lines produced using Allele’s methods are easier to maintain and use when compared to alternative pluripotent stem cells. In addition to internal projects, these iPSC lines and cell fate manipulation methods will be available via partnerships and licensing, providing companies with the most advanced iPSC technologies to further their therapeutic programs.