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NIA Small Business Showcase: DTx Pharma

Banner signifying OSBR handbookRNA medicines—small interfering RNA (siRNA) and antisense (ASO)—represent a versatile class of drugs for reducing expression of essentially any target gene implicated in disease. However, RNA medicines have difficulty entering cells and therefore require high concentrations for activity, leading to dose-limiting toxicities in the liver, kidney, marrow, and other tissues. DTx Pharma has addressed this issue by developing a platform that greatly improves the cellular entry and pharmacokinetics of RNA medicines, making delivery possible to virtually any tissue, including the central nervous system (CNS). The NIA-supported program highlighted here uses DTx’s delivery technology to target the tau gene/protein, a driver of brain degeneration in Alzheimer’s disease (AD) and rare diseases such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). Scientists and clinicians have suggested that reducing tau protein in the brain might slow or prevent neurodegeneration in these conditions.

The letters D,T, and X written out with Pharma underneathDTx aims to reduce tau expression by identifying highly active siRNA sequences targeting tau mRNA and directly attaching them to specific fatty acid structures (motifs) designed at DTx Pharma. DTx’s fatty acid motifs improve both cellular uptake by neurons and in vivo pharmacokinetic/pharmacodynamic (PK/PD) properties to make siRNA-mediated therapeutic gene knockdown feasible in the CNS. For its tau program, DTx is focusing on the use of siRNA rather than ASO, because of the long duration of action and more favorable safety profile of siRNA drugs. This delivery approach works for many different therapeutic applications and is thus a platform technology.

DTx is a platform therapeutics company working in multiple therapeutic areas, including the field of rare diseases but also in large markets with clear unmet need, such as those for Alzheimer’s disease. For perspective on the market, Alnylam Pharmaceuticals has technology that enables delivery of RNA medicines to one cell type in the liver, has one approved therapeutic, and is worth $14 billion as of June 2020. The company or companies that enable this class more broadly are likely to meet or exceed this valuation, given the breadth of opportunities for genetic medicines in other cell types and tissues.

Incumbent technologies for delivery of siRNA include lipid nanoparticles (LNPs) and conjugation to GalNAc, a polymeric sugar that allows for siRNA entry into hepatocytes. LNPs have been problematic in clinical studies, requiring premedication with steroids and diphenhydramine (Benadryl) to prevent serious reactions.

Biodistribution is also limited, with the bulk of material going to the liver. For these reasons, most companies have abandoned this approach. GalNAc has proven a safe and effective approach for delivering siRNA to the liver but is not helpful for any other anatomic site. DTx’s fatty acid conjugation technology allows for safe and effective targeting of multiple tissues of interest, including skeletal muscle, heart, lung, adipose, and immune tissues, in addition to neuronal tissues. A broad solution to RNA medicine delivery that includes many tissues of therapeutic interest offers significant economic potential. There are other competing technologies in development, including conjugation of siRNA to specific antibodies that target cell-surface receptors. Some of these approaches may allow for more selective delivery, but the technical hurdles for antibody-based programs are not trivial.

The DTx approach to targeting the tau gene differs from antibody approaches in that it reduces tau protein by turning off production by cells, targeting both intracellular and extracellular tau protein, while antibody approaches can target only extracellular tau.

Companny Milestones

Scientific

  • 2018: Generating and testing more than 150 specific fatty acid motifs for activity in delivery and in vivo distribution of siRNA and ASO, with testing results revealing critical structure/activity relationships that are DTx’s core intellectual property and technology.
  • 2018: Identifying fatty acid motifs that allow for cellular uptake of siRNA by multiple cell types and tissues of therapeutic interest.
  • 2019: Demonstrating in vivo biodistribution and activity of siRNA conjugated to specific fatty acid motifs.
  • 2020: Demonstrating activity of fatty acid–conjugated RNA medicines in mouse models of retinitis pigmentosa and Duchenne muscular dystrophy.
  • 2020: Reporting on the activity of DTx molecules in nonhuman primate studies expected.

Business

  • 2018: Received a seed round convertible note to assemble the core team and start experimental work developing a delivery technology platform. Resident company in JLabs San Diego. Recognized as a “Cool Company” by San Diego Venture Group and a graduate of the Springboard Program of Connect San Diego.
  • 2019: Received its first NIH and foundation grants. Series A financing completed. Filed first patent applications on foundational technology.
  • 2020: Expects to nominate the first lead therapeutic candidate for an inherited retinal disease and apply for orphan drug designation.

Financial Overview

  • 2018 seed financing raised more than $2,000,000 from friends and family, pharmaceutical veterans with experience in the RNA medicines space, and San Diego Tech Coast Angels.
  • 2019 Series A financing raised more than $10,500,000, led by Friedman Bioventure Fund 1, including Eli Lilly and Company, Viva Biotech Ltd., and multiple smaller funds and individual investors associated with Tech Coast Angels.
  • DTx has been awarded more than $1,000,000 in grant funding to date, with three active SBIR Phase I grants (NIA, National Center for Advancing Translational Sciences) and two foundation awards (the CMT Research Foundation and the Tau Pipeline Enabling Program of the Alzheimer’s Association/Rainwater Charitable Foundation).
  • DTx expects to initiate a Series B fundraising round as early as fall 2020. The expected round size will be a minimum of $50 million to support (1) internalization of chemistry efforts in oligo synthesis and conjugation; (2) development of a candidate targeting inherited retinal disease, including investigational new drug (IND)–enabling studies and a Phase I clinical trial; (3) development of a candidate targeting inherited muscle disease, including IND-enabling studies and a Phase I clinical trial; and (4) continued iteration on platform technology, including design and testing of new motifs for cellular tropism and pharmacokinetic enhancement.
  • DTx is in active discussion with potential pharmaceutical partners in multiple therapeutic indications. Should these discussions be successful, fundraising plans for the Series B round are likely to evolve.
  • DTx may open a convertible note vehicle before the Series B round to accommodate existing investor interest. Proceeds would be used to advance the first clinical candidate more rapidly through IND-enabling preclinical studies.

Intellectual Property

DTx has identified a series of fatty acid motifs composed of long chain fatty acids that allow for cellular uptake and improved pharmacokinetics when coupled with siRNA. The core intellectual property (IP) demonstrates a series of nonobvious structure–activity relationships that are important for cellular uptake, biodistribution, and activity of siRNA–fatty acid conjugates. Additional IP covers therapeutic uses of technology for targeting specific genes or tissues.

Product Development and Regulatory Strategy

DTx is a preclinical pharmaceutical company with a platform technology for delivery of RNA medicines. The company is pursuing a dual-track strategy of advancing its own lead therapeutic candidates in select indications (inherited retinal disorders, muscle disorders) into IND-enabling work and early clinical development while simultaneously engaging with established pharmaceutic companies with interest in licensing the technology for their own internal programs. The regulatory strategy follows the same pathway as other pharmaceutical companies developing novel chemical entities, including the full toxicity, stability, and chemistry, manufacturing, and controls assessments needed to support an IND filing. One of the company’s founders is an expert in the safety and development of oligonucleotide therapeutics and has been involved in several of the approved antisense studies.

Commercialization Strategy

DTx intends to pursue a dual track of advancing its own wholly owned medicines into the clinic, raising the capital needed to advance further based upon data generated in trials, and partnering with larger pharmaceutical companies that would either license the technology for an internal RNA medicine or take over development of a DTx-developed asset.

Company Details

DTx Pharma website

10655 Sorrento Valley Road
Suite 100
San Diego, CA 92121

Industry: Therapeutics

Management Team:

  • President, Chief Executive Officer, and Chief Scientific Officer: Arthur Suckow, Ph.D.
  • Chief Technology Officer: Guriq Basi, Ph.D.
  • Vice President of Chemistry: Charles Allerson, Ph.D.
  • Chief Operating Officer: Jeff Friedman, M.D., Ph.D.

Point of Contact:
Arthur Suckow, Ph.D.
Email Arthur Suckow
732-690-2035

Conference Selected for Showcase: BIO Digital (June 2020)