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enable immunotherapies in solid tumours

BY LAUNCHING NEW ADVANCED THERAPY VENTURES IN PARTNERSHIP WITH
ABOUT DSV

Deep Science Ventures is creating a future in which both humans and the planet can thrive.

We use our unique venture creation process to create, spin-out and invest into science companies, combining available scientific knowledge and founder-type scientists into high-impact ventures.

We operate in 4 sectors: Pharmaceuticals, Energy, Agriculture and Computation, tackling the challenges defining those areas by taking a first principles approach and partnering with leading institutions.

 

The Challenge

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

The incentivisation structure of R&D leads to the bulk of focus being on finding the next target (TIM3, LAG3, TIGIT, VISTA or one of many cytokines and other up / down regulating messengers) or new combinations thereof. Running another trial with the best-in-class immunotherapy at the time, sometimes stratified appropriately, but often not, and often leading to the same result. Either it works in a subset of patients briefly but ultimately leads to resistance, or fails completely. Over time clinicians will work out which combinations work the best but is this linear approach really the best way of exploring a highly complex and evolving space?

 

Our take on building new ventures in this space

We need entirely new strategies for combating solid tumours that consider the whole system from the outset which includes the tumour but also its microenvironment.

How can we move the focus away from blocking singular targets systemically and create therapeutics that learn and adapt with their environment – addressing both the adverse microenvironment and cancerous cells where a sufficient number of signals indicate a diseased state, at the same time sparing ‘healthy’ inflammation?

Some of the advances in 4th gen CAR-Ts are a step in this direction, utilising several different methods, including logic gates, to increase specificity and release of cytokines. How could some of this thinking be extended to the immune system, enhancing components that will be beneficial in combating cancer whilst inhibiting those that aren’t through leveraging the broader synbio toolkit and research in the dynamics of complex systems? This is one of our starting points for exploring this space. If that resonates with you and you work in any of these fields you can find out more about what you can engage here.

 

Join us to build these ventures

You’ll join DSV as a Founding Analyst (fixed contract, full-time) and work with us for 9-12 months to further refine the approaches. At the end of the 9-12 month period you will have helped to design and spin-out one or more ventures, and will become a full-time Founder of one of them.

Taking up a Founding Analyst (FA) role at DSV differs quite significantly from the entrepreneur in residence (EIR) role in other funds or venture studios. Instead of scouting for existing technologies which might overcome a specific challenge, an FA starts with identifying the areas where there is neglect or repeated failure yet potential solutions exist if considered from a different perspective, mapping the limitations to existing approaches at the specific and macro-level and considering the constraints of the broader ecosystem (capital, expertise, IP, knowledge, competition). You will start to build a company, iteratively determining the optimal solution for the problem.

 

Our offer

We provide a monthly salary (at a pre-seed stage startup level) to bridge the gap between developing the concept and getting it to an investable company stage. You and your Co-Founder(s) will own 80% of the new venture at inception and the pre-seed investment capital is already secured from DSV. Cancer Research UK-Therapeutic Discovery Laboratories will bring deep expertise in the space, apply time from their own staff to assist with the venture development process and – subject to investment committee decision – invest in cash and/or kind in the new venture(s) through providing lab FTE or facilities at their site on the Babraham Research Campus.

 

Our impact

We’ve so far built from scratch and invested in 9 brand new companies in the curative therapeutics space, including the three oncology ventures we built last year in partnership with Cancer Research UK – read our Founder stories here.

 

Who should apply

We’re after a broad technical expertise across immunology, immuno-oncology, synthetic biology and complexity or a comparable mathematical / physics field.

 

The ideal candidate would have experience in at least two of the following:

 

Broad areas: Immune suppression, immune excluded and immune inflamed environments, Immune infiltration, Immune-cancer checkpoints, immunomodulators, immune system activation, differentiation.

Specifically:
Messengers: Cell signaling, chemokines and cytokines, vascular factors, mediators and stromal-based inhibition, modifying transcriptional state, preventing cytokine storms.
Immune cell subtypes’ differential response to the microenvironment particularly natural killer cells, dendritic cells, T-regs, tumor-infiltrating lymphocytes and memory cells.
Known checkpoint targets: PD1, PD-L1, TIM3, LAG3, TIGIT, VISTA and checkpoint influencing factors: WNT, JAK2, CTLA4, CD4/8 balance, mutational load, chronic inflammation

 

Broad areas: Synthetic biology / genetic modification.

Specifically:
Epigenetic modification, receptor engineering / reprogramming immune cells, Notch receptor type systems, other boolean logic gates and arithmetic, toggle switches, kill switches, oscillators, CRISPR/Cas, Zinc Fingers more generally. Reprogramming metabolic pathways and genetic programmes and circuit modification more broadly, specific areas of transcription, protein expression, genetic circuits and signal transduction.

 

Broad areas: Complexity or relevant mathematical / physics field.

Specifically:
Complexity broadly, systems biology, adaptive systems, the interactome, genetic interaction, protein-protein interaction, analysis of network structure and temporal and spatial patterns, mapping and modification of complex dynamic states in any context.

ABOUT DSV

Deep Science Ventures is creating a future in which both humans and the planet can thrive.

We use our unique venture creation process to create, spin-out and invest into science companies, combining available scientific knowledge and founder-type scientists into high-impact ventures.

We operate in 4 sectors: Pharmaceuticals, Energy, Agriculture and Computation, tackling the challenges defining those areas by taking a first principles approach and partnering with leading institutions.

 

The Challenge

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

The incentivisation structure of R&D leads to the bulk of focus being on finding the next target (TIM3, LAG3, TIGIT, VISTA or one of many cytokines and other up / down regulating messengers) or new combinations thereof. Running another trial with the best-in-class immunotherapy at the time, sometimes stratified appropriately, but often not, and often leading to the same result. Either it works in a subset of patients briefly but ultimately leads to resistance, or fails completely. Over time clinicians will work out which combinations work the best but is this linear approach really the best way of exploring a highly complex and evolving space?

 

Our take on building new ventures in this space

We need entirely new strategies for combating solid tumours that consider the whole system from the outset which includes the tumour but also its microenvironment.

How can we move the focus away from blocking singular targets systemically and create therapeutics that learn and adapt with their environment – addressing both the adverse microenvironment and cancerous cells where a sufficient number of signals indicate a diseased state, at the same time sparing ‘healthy’ inflammation?

Some of the advances in 4th gen CAR-Ts are a step in this direction, utilising several different methods, including logic gates, to increase specificity and release of cytokines. How could some of this thinking be extended to the immune system, enhancing components that will be beneficial in combating cancer whilst inhibiting those that aren’t through leveraging the broader synbio toolkit and research in the dynamics of complex systems? This is one of our starting points for exploring this space. If that resonates with you and you work in any of these fields you can find out more about what you can engage here.

 

Join us to build these ventures

You’ll join DSV as a Founding Analyst (fixed contract, full-time) and work with us for 9-12 months to further refine the approaches. At the end of the 9-12 month period you will have helped to design and spin-out one or more ventures, and will become a full-time Founder of one of them.

Taking up a Founding Analyst (FA) role at DSV differs quite significantly from the entrepreneur in residence (EIR) role in other funds or venture studios. Instead of scouting for existing technologies which might overcome a specific challenge, an FA starts with identifying the areas where there is neglect or repeated failure yet potential solutions exist if considered from a different perspective, mapping the limitations to existing approaches at the specific and macro-level and considering the constraints of the broader ecosystem (capital, expertise, IP, knowledge, competition). You will start to build a company, iteratively determining the optimal solution for the problem.

 

Our offer

We provide a monthly salary (at a pre-seed stage startup level) to bridge the gap between developing the concept and getting it to an investable company stage. You and your Co-Founder(s) will own 80% of the new venture at inception and the pre-seed investment capital is already secured from DSV. Cancer Research UK-Therapeutic Discovery Laboratories will bring deep expertise in the space, apply time from their own staff to assist with the venture development process and – subject to investment committee decision – invest in cash and/or kind in the new venture(s) through providing lab FTE or facilities at their site on the Babraham Research Campus.

 

Our impact

We’ve so far built from scratch and invested in 9 brand new companies in the curative therapeutics space, including the three oncology ventures we built last year in partnership with Cancer Research UK – read our Founder stories here.

 

Who should apply

We’re after a broad technical expertise across immunology, immuno-oncology, synthetic biology and complexity or a comparable mathematical / physics field.

 

The ideal candidate would have experience in at least two of the following:

 

Broad areas: Immune suppression, immune excluded and immune inflamed environments, Immune infiltration, Immune-cancer checkpoints, immunomodulators, immune system activation, differentiation.

Specifically:
Messengers: Cell signaling, chemokines and cytokines, vascular factors, mediators and stromal-based inhibition, modifying transcriptional state, preventing cytokine storms.
Immune cell subtypes’ differential response to the microenvironment particularly natural killer cells, dendritic cells, T-regs, tumor-infiltrating lymphocytes and memory cells.
Known checkpoint targets: PD1, PD-L1, TIM3, LAG3, TIGIT, VISTA and checkpoint influencing factors: WNT, JAK2, CTLA4, CD4/8 balance, mutational load, chronic inflammation

 

Broad areas: Synthetic biology / genetic modification.

Specifically:
Epigenetic modification, receptor engineering / reprogramming immune cells, Notch receptor type systems, other boolean logic gates and arithmetic, toggle switches, kill switches, oscillators, CRISPR/Cas, Zinc Fingers more generally. Reprogramming metabolic pathways and genetic programmes and circuit modification more broadly, specific areas of transcription, protein expression, genetic circuits and signal transduction.

 

Broad areas: Complexity or relevant mathematical / physics field.

Specifically:
Complexity broadly, systems biology, adaptive systems, the interactome, genetic interaction, protein-protein interaction, analysis of network structure and temporal and spatial patterns, mapping and modification of complex dynamic states in any context.

Interviews ongoing for a full-time start in asap

Interviews ongoing for a full-time start in asap