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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Contact

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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.

Curative approaches for inflammatory disease

Problem to solve

Immune-mediated inflammatory diseases (IMIDs) encompass a range of chronic and debilitating disorders that together affect 3-7% of the global population. We still don’t understand exactly what causes most IMIDs, but know that it usually involves a complex interplay between genetic susceptibility and environmental triggers. While the treatment landscape for IMIDs has been transformed over the past two decades, therapeutic responses are still often incomplete, occur in only a subset of patients, lead to drug resistance, or incur significant side effects. There are still no cures, and long-term drug-free remission is rare.

Reason to solve

The clinical and economic impact of IMIDs is tremendous and steadily increasing globally. The market for anti-inflammatory drugs alone is expected to reach $165 billion annually by 2030, underscoring the great need for novel approaches with transformative efficacy. To achieve this, we must find ways to durably restore immune homeostasis – turning off the causal upstream sources of inflammation rather than simply mopping up downstream inflammatory signals. How can we leverage recent advances in single-cell-, systems- and synthetic-biology to dissect the complexity of IMIDs, and develop curative therapies that address root causes, tailored to the needs of individual patients?

Curative Approaches using Immune Strategies in Paediatric Oncology

Problem to solve

Childhood cancers are rare and heterogenous; however, their collective impact is significant, whereby they remain a top cause of death. In addition to the rapid progression of their primary tumours and frequent metastases, many proceed to develop secondary cancers. Moreover, high doses of chemotherapy and radiation can result in neurocognitive, developmental, and fertility defects later in life.

Reason to solve

Historically, children have been treated using the same modalities as for adults. However, their genetic and immunological makeup differs greatly and there is a significant need for more tailored therapeutics. Can we exploit some of these unique characteristics and commonalities to devise a curative solution across multiple paediatric indications?

Available opportunities

Co-Founder, Curative Therapies for Inflammatory Disease

Pharmaceuticals
See job description

Co-Founder in Residence, Immune-Related Therapeutics for Paediatric Cancer

Pharmaceuticals
See job description

Co-Founder, next generation therapeutics for Parkinson's (Open Application)

Pharmaceuticals
See job description

Founder in Residence, Next Generation Therapeutics for Parkinson's

Pharmaceuticals
See job description

Associate, New Venture Creation in Curative Therapeutics (Open Application)

Pharmaceuticals
See job description
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

Deliver

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
Enhancing Tregs to restore balance in inflammatory disorders

Bastion Therapeutics

Opportunity

Autoimmune diseases arise from an overactive immune system attacking healthy cells, leading to chronic inflammation and tissue damage. Current treatments involve broad immunosuppression, risking serious side effects. Treg cell therapy offers precise immune regulation and this strategy holds the potential to revolutionise autoimmune disease treatment with improved safety and efficacy.

Solution

Bastion Therapeutics leverages the proprietary GRIT™ platform technology to enhance Tregs to modulate the immune system and overcome challenges associated with previous generations of Treg therapies. Our vision is to provide life-changing therapies that are efficacious, durable and safe to patients suffering from Inflammatory Disorders.

  • 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
  • Series A
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
  • cancer

Revolutionising Paediatric Cancer Treatment

We believe there is a significant opportunity to revolutionise the way we treat paediatric cancer patients, by taking a paediatric-first approach.

15 February 2024
  • pharmaceuticals
  • partnerships

Forging New Pathways in Parkinson’s Therapeutics

We announce our alliance with Parkinson's UK.

20 December 2023
  • pharmaceuticals
  • Neurofibromatosis

Gene Therapy for Neurofibromatosis - the Path to a Cure

Despite being among the most common genetic disorders worldwide (1 in ~2500 births collectively) the NF field has sadly been overlooked for decades. Yet it is difficult to understand why, given the huge unmet need and extremely limited treatment options – none of which offer curative potential for patients. Gene therapy offers the path towards a cure. In this article, we outline the nature of the challenge, why now is the right time to solve it, and explore the unanswered questions we'd like to address through venture creation. 

08 August 2023
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