Pharma

Curative Therapeutics

Creating ventures to cure diseases, using emerging combinatorial techniques
The current rate of therapeutic failure is unsustainable and unnecessary, often attributed to poor disease models or a lack of specificity. The emergence of personalised and precision therapeutics creates the opportunity to cure diseases by addressing the root causes directly.

There are only a small number of diseases in which intervention at a single point, common across all patients, can sufficiently and persistently alter the system towards a healthy state. Most diseases consist of a complex set of dynamic failures from genetics and epigenetics to neural activity: these differ across patients, within patients and over time. Trials often fail because the models used to demonstrate effectiveness in preclinical studies don’t accurately reflect the underlying causes, which can vary substantially across diseases and patients, and endpoints in trials often measure symptoms.

Our approach to creating curative therapeutic companies focuses on four themes: effectively leveraging computational approaches to address complexity; developing therapeutics that can compute in-vivo and respond dynamically to the changing internal environment; creating better systems, models and analytics to support therapeutic discovery and development; and a focus on the root cause, including fixing and buffering molecular level damage, fixing broken or unhelpful messaging and signalling pathways, correcting errors at every level of gene expression and modifying the state of cells to drive regeneration.

Thank you!

Contact

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Areas of venture creation:

Curative Approaches in Cystic Fibrosis

Problem to solve

Cystic Fibrosis (CF) is one of the most common genetic diseases. In patients with CF, alterations in the gene encoding CFTR, a chloride channel, cause the body to produce a thick and sticky mucus that can clog the lungs and obstruct the pancreas. CF can be life-threatening, and people with the condition tend to have a shorter-than-normal life span. For a curative genetic therapy for CF, delivery is key. Although the most life-threatening symptoms of CF occur in the lung, CF is a systemic disease. To tackle the disease in all affected tissues, we will need to deliver a therapy to multiple tissues whilst ensuring the therapeutic agent reaches the lung in sufficient concentrations.

Reason to solve

The mutational profile across CF patients is complex and while life-extending therapies exist for the most common mutations, large patient populations don’t benefit from these therapies, and disease-modifying therapies are lacking.

Tackling immune suppressed solid tumours

Problem to solve

Immunotherapies, especially checkpoint inhibitors and CAR-T cells, have revolutionised cancer treatment with incredible results in a subset of solid tumours and blood-based cancers, respectively. Despite this widely recognised success and paradigm shift in oncology, these therapies still only increase patient survival by limited degrees, often only 10-20% versus chemotherapies, or work in selected patient subsets. Importantly, resistance to these therapies is already developing due to selective pressure on the cancer to evade this method of immune detection, leading to resistance initially and, later, recurrence. We are still very far from immunotherapeutics that work across all cancers, or in all patients.

Reason to solve

We need entirely new strategies for combating solid tumours that consider the whole system from the outset: both tumour and microenvironment. We need to shift the focus away from blocking singular immune-regulatory targets systemically, towards creating therapeutics that learn and adapt with their environment – addressing the malignant tumour cells and adverse microenvironment, while sparing ‘healthy’ inflammation. Some advances among 4th gen CAR-T cells are a step in this direction, but how could this thinking be extended to other immune players – enhancing beneficial components while inhibiting problematic ones, through leveraging the broader synbio and sysbio toolkits?

Moving cell therapies into the mainstream

Problem to solve

With recent advances in cell and gene therapies it feels like cures to some of mankind’s most devastating diseases are within reach. CAR-T therapies can now cure some leukaemias and the first approved gene therapies are reversing some of the effects of rare diseases. This promise of a potential cure, combined with technological advances, has stimulated a lot of investment in the advanced therapies space. However, major hurdles still need to be overcome for cell and gene therapies to deliver on that promise and become mainstays of medicine in multiple therapeutic areas.

Reason to solve

We need to find more efficient ways to generate cellular therapies. Many existing cell therapies use autologous sources (and therefore can’t be scaled up), and those that use allogeneic sources tend to require expensive reagents and lengthy protocols to differentiate cells, but still end up with a sub-optimal product. If we could develop analytical systems to evaluate pluripotent and multipotent cells, and then use that information to optimise differentiation methods, including through leveraging the array of synbio technologies now at our disposal, we could generate numerous therapeutic products at scale. This would revolutionise our ability to develop cell therapies across a variety of diseases with high unmet need.

Reducing liver toxicity from vectors used in gene therapies

Problem to solve

Gene therapies can systemically treat severe genetic diseases. A gene therapy for spinal muscular atrophy is already approved and in use, and numerous others are in development. However, many of the gene therapy vehicles are toxic, particularly to the liver. These toxicities reduce the dose we can use, which can prevent the therapy from working. In some clinical trials, toxicities have led to deaths and trial suspension.

Reason to solve

We need to reduce the liver toxicity associated with viral gene delivery vehicles. Could we find a way to shield or hide the liver from these viruses, so that the virus can’t infect the liver? By reducing the liver toxicity, it’s possible that higher doses could be used, thereby expanding the therapeutic window for multiple viral delivery vehicles. Solving liver toxicity could unlock the potential for viral gene delivery.

Available opportunities

Associate, New Venture Creation in Therapeutics

Pharmaceuticals

Founder, Bioinformatics for Cell-based Therapeutics

Pharmaceuticals

Keith Thompson

MBE - Founder of the Cell and Gene Therapy Catapult

When I retired from the Catapult, I made a golden rule to only work with inspiring people, on interesting things. DSV's model for innovation works in areas where others have failed, creating companies with strong foundations and mitigating execution risk. The portfolio has several companies that quite simply make you sit up and take notice - seeing them grow from founding to series A is an exciting prospect.

Our companies

  • pharmaceuticals
  • Pre-seed
Next generation synthetic lethality

Opportunity

Solution

  • pharmaceuticals
  • Pre-seed
Viral immunotherapy optimised for systemic delivery

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Solution

  • pharmaceuticals
  • Pre-seed
Engineered bacteria to disrupt the tumour microenvironment

Opportunity

Solution

  • pharmaceuticals
  • Seed
Next generation CAR-Ts, taking cell therapy into in vivo

Opportunity

Solution

  • pharmaceuticals
  • Seed
Unlocking microbiome through bacteriophage

Opportunity

Solution

  • pharmaceuticals
  • Seed
Diagnosing and treating microbiome diseases before symptoms start

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  • pharmaceuticals
  • Seed
A breakthrough strategy for neuroprotection

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Solution

  • pharmaceuticals
  • Seed
Predicting the evolution of cancer

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Solution

  • pharmaceuticals
  • Seed
Fully automated cell manufacturing platform

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Solution

  • pharmaceuticals
  • Seed
Making surgery safer

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Solution

  • pharmaceuticals
  • Seed
One day de novo antibody design

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Solution

  • pharmaceuticals
  • Seed
Energy efficient, scalable bioprocessing

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Solution

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