Sustainable Differentiation & Competitive Advantages

Our potential to become the most impactful company in the gene therapy industry for patients is driven by three unique value drivers at 4DMT:

ROBUST, INDUSTRY-LEADING GENE THERAPY VECTOR DISCOVERY PLATFORM: Our Therapeutic Vector Evolution platform is able to generate highly optimized, customized and proprietary AAV vectors for any tissue or cell type in the body. This empowers us to develop superior products, and to create products to target many diseases that cannot be addressed adequately with the current 1st and 2nd generation naturally-occurring (primitive) AAV vectors. Our co-Founder Dr. David Schaffer pioneered this platform at UC Berkeley for roughly 15 years prior to the formation of 4DMT. At 4DMT we have industrialized this discovery platform by creating over 30 unique AAV vector “libraries” comprising over 100 million vectors, building out discovery capabilities in vivo and in human organotypic models ex vivo. We’ve taken this technology to a whole new level. Over the next decade, our goal is to make 4DMT vectors the gold standards for the industry.

EXTENSIVE DEVELOPMENT EXPERTISE WITH VIRAL VECTOR GENE THERAPEUTICS: Our team has deep leadership experience translating viral vectors into the clinic, and developing them in well-designed and executed clinical trials. Dr. Kirn has led clinical R&D programs with 10 different viral vector products, involving six different vector platforms, over 30 clinical trials, and over 800 patients with life-threatening diseases. Dr. Francis and Ms. Janke have led over 10 clinical trials (Phase 1 – 3) with multiple products in the field. This combined clinical-regulatory experience will accelerate the development of our 4DMT products and increase the likelihood of success.

DIVERSIFIED, SUSTAINABLE AND EFFICIENT BUSINESS MODEL: The value of our business is driven by our product pipeline. Each 4DMT product will be developed and commercialized along one of three different tracks. First, we will develop and commercialize a number of products ourselves. Second, for some products we enter into co-development partnerships with complementary biopharmaceutical companies. Third, in some cases we will out-license the use of our customized vectors for the delivery of specific transgene payloads for the treatment of diseases that 4DMT will not be pursuing ourselves. To date we have partnerships with the following leading pharmaceutical companies:

  • Roche
  • Pfizer
  • Medimmune-Astra Zeneca

4D Sustainable Competitive Advantages

4DMT 3rd-generation AAV vectors have important advantages that differentiate them from currently available vectors, including commonly used naturally-occurring primitive vectors such as AAV2, 5, 8, 9:

THE 4DMT TARGET VECTOR PROFILE – THERAPEUTIC VECTOR EVOLUTION RESULTS IN SUPERIOR AAV VECTORS DESIGNED FOR ENGINEERING INTO SUPERIOR PRODUCTS FOR ANY DISEASE: Customization for specific target tissues for each optimal treatment of each diseaseNaturally occurring vectors such as AAV2, AAV8 and AAV9 were discovered as lab contaminants or monkey infections. In contrast, 4DMT vectors are discovered through Therapeutic Vector Evolution for delivery to a specific tissue by the optimal clinical route of administration; we refer to these vector specifications as the “Target Vector Profile” which we generate with the target disease in mind.

  • 4DMT AAV Variant Libraries comprised of over 100 million variants: We select our vectors according to a Target Vector Profile from a pool of over 100 million novel 4DMT variants that were created by over 30 different molecular biology methods (each method comprises a vector “library”). In contrast, our competitors use vectors that were selected from a handful of naturally occurring vectors. 4DMT vectors are therefore selected from a proprietary vector pool estimated to be 10 million times more diverse than the few used by most in the field.
  • Natural Selection is a powerful force to identify the best variants for any disease target: Optimization for delivery to target tissues at multiple steps in the pathway from the syringe all the way to target cells results in superior vectors for any specific disease. Because Therapeutic Vector Evolution allows nature to select the best vector capsids for delivery to the target tissue in vivo (natural selection), our vectors therefore can be optimized at multiple complimentary steps throughout the entire pathway.

SAFETY – VECTOR TARGETING, SELECTIVITY AND IMPROVED SAFETY PROFILE: Vector targeting to specific tissues and cells according to the Target Vector Profile can translate into less off-target delivery to non-target tissues, leading to lower risks of toxicity and inflammatory responses.

EFFICACY – VECTOR DELIVERY IMPROVEMENTS ARE DESIGNED FOR MORE EFFECTIVE PRODUCTS: 4DMT vectors are highly targeted to specific tissues, leading to improved delivery and engineering for superior product efficacy.

ANTIBODY RESISTANCE: 4DMT vectors can be selected for resistance to pre-existing antibodies in any given patient population. This should translate into better delivery, better efficacy and more patients amenable to treatment. In contrast, standard available vectors can often be neutralized in a majority of patients in the population, and more than 50 percent of patients are excluded from some intravenous dosing trials due to their pre-existing AAV antibodies.

MANUFACTURING ADVANTAGES: 4DMT vectors are selected according to a Target Vector Profile that includes high productivity manufacturing using scalable unit operations, including purification by column chromatography. Therapeutic Vector Evolution selects for vectors with high manufacturing efficiency. In addition, manufacturing risks can be reduced because our vectors are “evolved” for delivery to target tissues at lower doses than 1st or 2nd generation AAV.

STRONG COMPOSITION-OF-MATTER PATENTABILITY:  4DMT vectors are selected from a proprietary pool of roughly 100 million novel variants. Composition-of-matter patent claims are filed on each unique variant discovered. In contrast, the patentability of naturally occurring serotypes may be limited in some cases.

LEADERSHIP IN DIRECTED EVOLUTION AND THERAPEUTIC VECTOR EVOLUTION:  Directed Vector Evolution was pioneered by our co-Founder Professor David Schaffer at UC Berkeley over a 15 year period. Over $15 Million dollars of grant funding supported the initial development of this vector discovery platform. At 4DMT, we’ve industrialized this technology to create the Therapeutic Vector Evolution discovery platform. In addition to Dr. Schaffer’s expertise as CSO, 4DMT has hired experienced personnel from Dr. Schaffer’s lab. Finally, the 4DMT AAV variant pool consists of over 100 million novel variants. To our knowledge, this is the largest and most diverse variant library in the world. Our vectors have been constructed by over 30 different molecular methodologies in order to maximize diversity. We therefore have the expertise, the personnel and the resources to maximize the potential of this discovery platform.