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.

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Areas of venture creation:

Curative approaches in Neurofibromatosis

Problem to solve

Neurofibromatosis (type 1 & 2) and Schwannomatosis are a group of devastating genetic diseases which lead to the formation of nerve sheath tumours, alongside a constellation of debilitating symptoms including chronic pain, vision and hearing loss, musculoskeletal disfigurement, cognitive defects, and increased risk of various cancers. Despite being more prevalent than cystic fibrosis, NF has been historically neglected. It currently attracts just one FDA-approved therapy (the MEK inhibitor, selumetinib, for NF1 tumours), which slows or modestly reverses tumour growth, but carries significant side effects, and as many as 30% of patients do not respond. As of yet, there are no cures for NF.

Reason to solve

The burden of NF is large and multi-dimensional, greatly impacting the quality and duration of patients' lives, while incurring disproportionately high costs to healthcare systems due to the frequent need for complex, life-long, multi-specialist care. Despite being monogenic, these diseases display extensive clinical and biological complexity, making them difficult to treat and cure. How can we exploit the recent emergence of new tools, modalities and datasets to overcome these challenges and develop curative therapies for NF patients?

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

Founder, Gene Therapy for Cystic Fibrosis

Pharmaceuticals
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Founder, Bioinformatics for Cell-based Therapeutics

Pharmaceuticals
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Co-Founder, Enabling Immunotherapies in Solid Tumours

Pharmaceuticals
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Associate, New Venture Creation in Therapeutics

Pharmaceuticals
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Explore careers

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

Enedra

Opportunity

Every cancer undergoes an evolutionary process which generates millions of mutationally and biologically diverse cells. As a result, synthetic lethality therapeutics raised against specific driver mutations only work in a limited subset of patients and only work until the cancer evolution strikes again, with drug resistance arising within a few months.

Solution

Enedra harnesses the power of Synthetic Lethality and Advanced Computational Systems Biology, to discover the first therapeutics that work against the complexity, biological and mutational heterogeneity of cancer.
  • pharmaceuticals
  • Pre-seed
Viral immunotherapy optimised for systemic delivery

Stratosvir

Opportunity

Therapeutic viruses offer huge potential to treat solid tumours but are typically destroyed rapidly by the patient’s immune system. Being limited to intratumoral injection, researchers have struggled for decades to safely and effectively harness this power, restricting their clinical use.

Solution

Stratosvir is developing improved viral immunotherapy, engineered to allow systemic delivery by avoiding immune clearance. This allows their cancer-killing virus to deliver medicinal payloads within the tumour to stimulate and reprogram the immune system to attack and destroy cancer.
  • pharmaceuticals
  • Pre-seed
Engineered bacteria to disrupt the tumour microenvironment

Neobe Therapeutics

Opportunity

Immunotherapy offers the potential to eradicate cancer, however today, only around 20% of patients with solid tumours can benefit from these cutting-edge treatments. Multiple factors contribute to this low level of efficacy, but chief among them is the existence of physical matrix barriers around the tumour that lead to the generation of an immune "excluded" microenvironment.

Solution

Neobe Therapeutics are harnessing the synthetic biology toolkit to engineer tumour-colonising bacteria that locally disrupt this microenvironment and enable the success of immunotherapies in current non-responders.
  • pharmaceuticals
  • Seed
Next generation CAR-Ts, taking cell therapy into in vivo

Immtune

Opportunity

CAR-T therapy is a form of cancer treatment. These therapies currently only work well in blood cancers (less than 4% of total cases) and require therapeutic cells to be modified and grown outside the body. This highly complex and expensive process doesn’t work for everyone, results in cells of variable quality, and treatments that costs hundreds of thousands of pounds.

Solution

ImmTune Therapies is developing therapies that allow the patient’s body to develop these therapeutic cells themselves; which is considerably cheaper, and produces more effective products.
  • pharmaceuticals
  • Seed
Unlocking microbiome through bacteriophage

Ancilia

Opportunity

The gut microbiome has been implicated in a number of chronic diseases. Bacterial therapies offer promise to restore the healthy composition of the gut and treat disease, but many of these therapies do not effectively populate the gut. One hypothesis is that this consistent failure is due to native bacteriophage that prey on live bacterial therapeutics introduced to the gut.

Solution

Ancilia are developing a new class of engineered bacterial therapies, resistant to pathological phages, that effectively alter the human to treat the growing number of diseases linked to the microbiome.
  • pharmaceuticals
  • Seed
Diagnosing and treating microbiome diseases before symptoms start

CC Bio

Opportunity

Current microbiome companies view the microbiome as either healthy or diseased but this is not reflective of the fact that microbiome diseases occur gradually over time.

Solution

CC Bio are using synthetic biology to sense the presence of harmful bacteria and produce targeted therapeutic products to neutralise them. Their automated discovery platform enables rapid identification and prototyping of similar technologies for multiple other disease indications (<4 weeks), including skin health, gut health and dental health, as well as drug metabolism.
  • pharmaceuticals
  • Seed
A breakthrough strategy for neuroprotection

Reflection Therapeutics

Opportunity

Neuroinflammation, or chronic inflammation in the brain, has a crucial role in many devastating diseases, including Alzheimer’s, Multiple Sclerosis and many rare illnesses affecting brain function. An innovative drug that effectively targets neuroinflammation will profoundly benefit these patients as well as capture a large share of an estimated $45Bn market.

Solution

Reflection Therapeutics is developing targeted anti-inflammatory cell therapies to reduce neuroinflammation, protect neurons and increase synaptic connectivity, which will prevent a decline in cognitive function.
  • pharmaceuticals
  • Seed
Predicting the evolution of cancer

ConcR

Opportunity

Treatment resistance is responsible for 90% of cancer related deaths and consumes approximately 30% of the total cancer care spend.

Solution

ConcR combines cutting edge machine learning techniques and knowledge of tumour progression. Concr’s software provides drug developers with insights on appropriate in vivo models, patient populations and stratification biomarkers, as well as giving clinicians evidence-based outputs of patient-specific cancer progression, enabling therapy adaptation before treatment resistance arises.
  • pharmaceuticals
  • Seed
Fully automated cell manufacturing platform

Mytos

Opportunity

A significant component of biotech is manual preparation and growth of cells. This is expanding exponentially as therapeutics themselves become cell-based, most notably in cancer treatment. This is not just a significant time sink, it often involves significant waste, scope for human error and limits reproducibility.

Solution

Mytos have developed a system to fully automate cell manufacturing. Each machine completes the work of 10 scientists, whilst also reducing wastage and improving consistency.
  • pharmaceuticals
  • Seed
Making surgery safer

Scalpel

Opportunity

Patient safety in surgery is a serious global public health concern. Approximately 42.7 million adverse events occur in patients annually, with at least 7 million people a year experiencing disabling surgical complications and each OR delay costing $7000-$8000 per operating room day. There is an urgent need to upgrade current operating theatres.

Solution

Scalpel integrates data from healthcare records, AI-based analytics, sensors within the operating room and clinical actions to improve patient safety and operating theatre efficiency.
  • pharmaceuticals
  • Seed
One day de novo antibody design

Antiverse

Opportunity

60% of therapeutics are antibody-based. The discovery process is often longer than 18 months and costs hundreds of thousands of pounds, largely based on trial and error: testing of “libraries” of millions of antibodies against the target to see what “binds”, with no guarantee that the library contains the desired antibody.

Solution

Using a combination of robotics, state of the art machine learning and cell-free protein synthesis, Antiverse aims to be the first company in the world capable of developing antibody drug candidates in one day for any given antigen.
  • pharmaceuticals
  • Seed
Energy efficient, scalable bioprocessing

uFraction8

Opportunity

The bio-economy holds enormous potential: everything from fuel to therapeutics and food can be produced in modified bacteria, algae and yeast. The existing challenge is the unscalable, energy-intensive separation process, with high up-front capital costs of centrifuges and operational expense of liquid particle separation (often more than a third of total cost of production).

Solution

uFraction8 provides massively scalable bioprocessing without pre-concentration steps, filters, membranes or flocculants. It does not clog, does not have a theoretical size limit and significantly reduces energy costs, which currently represent the highest proportion of costs for producers.
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Content
  • pharmaceuticals
  • Cystic Fibrosis

Creating Gene Therapies for Cystic Fibrosis

In this article, we outline how far gene therapies have come since they were first utilised in the early 1990s, how we're planning on using a promising approach to develop a curative therapy for Cystic Fibrosis, and how you can join us to make it a reality.

23 December 2022
  • pharmaceuticals
  • Partnerships

Optimizing for Outcomes: how fresh perspectives can solve complex diseases

Using our methodology of venture creation, we're able to uncover novel therapeutics approaches in a disease area, that often haven't previously been considered. In this article, we explain how this works in practice, and how we've worked with two partners, the Children's Tumor Foundation and the Cystic Fibrosis Foundation, to uncover approaches within Neurofibromatosis and Cystic Fibrosis respectively.

09 December 2022
  • pharmaceuticals
  • Partnership

Our Partnership with AbbVie

We've partnered with AbbVie, a global pharmaceutical company, to create ventures targeting immune-mediated inflammatory diseases. This content post contains the press release detailing the partnership.

30 November 2022
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