Five Cell and Gene Therapy Startups Present at First BioFoundry Incubator Showcase

[REPORT] Five Cell and Gene Therapy Startups Present at First BioFoundry Incubator Showcase

BioFoundry highlight five startups from their recent showcase event
Despite all of the challenges presented by the COVID-19 pandemic, excitement around cell and gene therapies continues unabated. That excitement is translating into significant funding. According to the Alliance for Regenerative Medicine, companies in the space raised a record $19.9 billion in 2020 – twice that in 2019 and well above the amounts garnered in the prior two years ($13.3 billion in 2018 and $7.5 billion in 2017).1
 
The BioFoundry program, a joint program between the Biopharma and Entrepreneurship and Commercialization Divisions of the New Jersey Innovation Institute (NJII), is helping promising early-stage ventures in biotechnology and innovative cell and gene therapies obtain some of that funding. Assistance is provided through one-on-one interactions, workshops and roundtables covering IP strategy, licensing and partnerships, hiring and team management and business development. The goal is to support participants as they prepare to pursue Series A funding by matching them with customized resources including capital, vetted talent, scale-up assets and mentoring.
 
Of 800 applicants that applied to the overall BioFoundry program, which was created in partnership with the Innovation Accelerator Foundation (IAF) and funded by the U.S. Economic Development Administration, 10 were selected to become members of the first “class”. Based on their compelling science and technology, the availability of their teams and their fundraising stage, five of these 10 were chosen to participate in the first incubator.
 
The program ran approximately 15 weeks and culminated in February 2021 with the BioFoundry Startup Incubator Showcase, during which each of the companies – Navega Therapeutics, TeraImmune, LEAH Labs, Ciscovery Bio and Nvigorea AB – gave presentations on their technologies, target markets and goals for the future.

Navega Therapeutics is a preclinical stage company developing a gene therapy platform for the treatment of chronic pain that is both highly specific and long-lasting. Approximately 30% of Americans live with some form of chronic pain, and the overall market opportunity for chronic pain is estimated to be $105 billion, according to Founder and CEO Ana Morena.
 
The technology targets the SCN9a gene associated with the NaV1.7 ion channel, which has been correlated with pain signalling. Attempts to inhibit the SCN9a gene have proven difficult using small-molecule drugs and antibodies. Navega is therefore pursuing the epigenetic repression of sodium channels for the treatment and prevention of chronic neuropathic pain.
 
A version of CRISPR called dCas9 that has no nuclease activity is used to design guide RNAs that target the gene of interest, and when combined with added repressors, block gene expression. Navega is also exploring the use of zing finger nucleases combined with repressors. In both cases, the therapy is delivered using adeno-associated viral vectors via intrathecal injection for targeted delivery to the dorsal root ganglia. A single injection of the highly specific, non-addictive gene therapy lasts for several months.
 
Navega has demonstrated proof of concept in several different animal models and will be targeting the orphan disease erythromelalgia as its first indication. Morena expects to have a lead candidate identified by the end of 2021, after which tox studies and CMC data development will begin. She hopes to initiate a Phase 1/2A clinical study by mid-2023 and then move into a Phase 3 trial in the larger chronic pain space.
 
To date Navega has raised $5 million and has had an initial meeting with the European Medicines Agency.

TeraImmune is developing innovative immune-cell therapies based on programmed regulatory T (Treg) cells that recognize and suppress unwanted immune reactions, including those that cause autoimmune diseases. The cells are engineered to target specific receptors, thus preventing unwanted side effects. 
 
The company’s proprietary TREGable™ and TREGing™ technologies make it possible to consistently produce disease-specific Tregs that retain their function in vivo, which has been a challenge for other technologies employed to date, according to TeraImmune Co-Founder and COO Jay Park.  
 
TeraImmune has also developed technology designed to target the B Cell Receptor (BCR) on the surfaces of neoplastic B cells. The proprietary B-cell Antibody Receptor (BAR) technology avoids the potential serious adverse events observed with CD19-targeted chimeric antigen receptor (CAR) therapies, such as cytokine release syndrome and neurological toxicity.
 
The treatment begins with collection of a patient’s blood. Treg cells are then isolated, engineered and expanded, and finally infused back into the patient’s body. Notably, TeraImmune’s platform can be customized to target a range of autoimmune diseases.
 
Four candidates in TeraImmune’s pipeline target diseases with a $78-billion market value. Its lead candidate for hemophilia A is at the preclinical stage. Other disease targets include multiple schlerosis, B cell lymphoma, xeno-transplantaiton and atopic dermatitis.
 
The company received a Small Business Innovation Research (SBIR) phase I grant in 2018 to support its hemophilia A program, concluded a successful Series A funding round and met with FDA in 2020 in preparation for filing of an IND application. Park is eager to speak with people interested in co-development, licensing and equity investment opportunities.

LEAH Labs is a seed-stage biotechnology company using modern gene-editing technologies to make affordable CAR T-cell therapies for the veterinary market. There are 6 million cases of cancer in dogs in the U.S. each year, and one-third of dogs die of cancer irrespective of size and age, according to Cofounder and CEO Wes Wierson. Current treatments (chemotherapy and radiation) are outdated, expensive (up to $15,000), noncurative and require 12-15 visits.
 
Wierson and his colleagues are leveraging the knowledge gained with human CAR T-cell therapies, several of which have been approved by FDA, for the treatment of canine B-cell lymphoma, which occurs in more than 250,000 dogs per year – a market value of approximately $1.5 billion.
 
Unlike current human CAR-T therapies, which are patient-specific (autologous), Leah Labs is developing an off-the-shelf (allogeneic) treatment using CRISPR gene-editing tools to both convert T cells into CAR-T cells that target and destroy tumor cells and knock out endogenous receptors in order to avoid host rejection. 
 
Another difference: LEAH Lab’s cell therapy is regulated by the U.S. Department of Agriculture. The company has already demonstrated efficacy in the lab. An initial pilot study is typically performed next to determine safety, followed by a 3-month clinical study, after which a clinical trial in which client-owned dogs are treated is necessary to show efficacy in comparison to an historical control. Overall, it will take just 2-3 years and an investment of ~$5 million dollars for LEAH Labs to bring this novel therapy to market.
 
Through a WeFunder campaign launched in August 2019 and SBIR and other grants, LEAH Labs has raised over $1 million. A pilot safety study was initiated in February 2021, and the company is funded through completion of the efficacy testing. Wierson would, however, like additional capital to support a concurrent optimal dosing study. The company will be launching a second WeFunder campaign soon. The goal is to have a product on the market by Q2 2024.
 
Ciscovery Bio is developing better methods for predicting whether drug candidates will be successful using non-coding biomarkers known as cis-regulatory modules (CRMs). These enhancers and promotors are the largest class of DNA elements in the noncoding genome – there are 0.5 to 1 million of them according to CEO Joonyul Kim. Importantly, they control gene expression and are responsible for 90% of gene expression variations.
 
The company’s GRAMc proprietary unbiased functional CRM discovery tool is, says Kim, the most comprehensive CRM discovery tool available. It is capable of simultaneously evaluating tens of millions of DNA fragments in a given cell type for CRM activity and has been shown to identify CRMs systematically missed by other tools.
 
Drug-induced liver toxicity is the major cause of drug failures in clinical trials and market withdrawals. The reason: current assays only examine a few cellular responses. Ciscovery Bio has shown in a pilot study using 4000 randomly selected CRMs from HepG2 cells, that it is able to distinguish drugs with and without liver toxicity, with the number of CRMs responsive to different drugs indicating the severity of the toxicity.
 
In addition, the company has developed a CRM-guided platform for the prediction of liver toxicity for combinations of drugs, which Kim notes is practically important but difficult to do. The company is also developing a CRM dataset that will enable the prediction of drug responses by individual patients and the prediction of drug combinations that can selectively kill cancer cells in specific patients.
 
Currently Ciscovery Bio is conducting genome-scale screening of 500 million data points to identify drug-responsive CRMs. Kim hopes to have a comprehensive in vitro liver toxicity test for use by drug discovery firms on the market in 2021. After raising additional capital in the fall, the company will build a CRM variants database for the development of a personalized cancer therapy strategy that will then be validated in animal models.
 
Uppsala University spinoff Nvigorea AB is commercializing the world’s first nanocellulose-based mille-feuille paper capable of removing all types of viruses, including the smallest and most resistant ones, from water or protein solutions. The total market for virus removal is $2.9 billion and growing at a compound annual growth rate of 12% – and supplied by just four companies, according to CEO and Founder Albert Mihranyan.
 
Nanofiltration using Nvigorea’s nanocellulose-based single-use device is an effective, scalable solution for the viral filtration of biologics, including viral vectors used for cell and gene therapies, from the lab to commercial scale, says Mihranyan. The paper filter consists of 100% cellulose nanofibers derived from naturally occurring Cladophora algae and produced using traditional, inexpensive and sustainable paper making processes.
 
Nvigorea can tailor the pore size distribution of the filter paper on the nanoscale with high precision and offers a range of different filter sizings and configurations that have been validated in studies performed jointly with top biopharma companies using real samples under real industrial manufacturing situations.
 
Mihranyan believes Nvigorea’s virus filter technology is a critical bioprocessing tool that provides high performance with unparalleled cost efficiency and has multiple potential applications, including the full spectrum of biological production requirements to point-of-use drinking water purification and the manufacture of non-pasteurizable protein-based products derived from foods.
 
Nvigorea is looking to out-license its platform to large scale manufacturers for scale up, but in the short term hopes to build of a pilot production facility to directly supply niche segments such as the cell and gene therapy market, where its filter technology can be used to ensure the biosafety of cell culture media and enable the cost-effective downstream purification of viral vectors. To achieve these goals, the company is seeking manufacturing partners for scale up, investors for shortening the time to market and biologics developers interested in joint bioprocess development projects.
 
The interest garnered by these five participants in the first BioFoundry Startup Incubator reflects the effort invested by NJII and the Innovation Accelerator Foundation. It has also created interest in additional programs. The BioVentures Exchange Network, or BVX for short, is a platform currently under development that will provide all applicants to BioFoundry programs a means for connecting to various program resources, companies involved in the biopharma ecosystem in New Jersey and one another. “BVX is another example of how we are working to bridge the gap between early-stage and established pharma companies in the state,” observes Catherine Tsavalas, Program Director for Entrepreneurship with NJII.
 
NJII is also planning a second BioFoundry Incubator program in October 2021 and will start recruiting nationally and even internationally (for companies planning to have a presence in the US) early in the summer.
 
Click here to watch the full video of pitches.

References
  1. Janet Lambert, Alliance for Regenerative Medicine 2021 Cell and Gene Therapy State of the Industry Briefing, January 13, 2021, http://alliancerm.org/wp-content/uploads/2021/01/SOTI-2021-pdf.pdf