Optimizing for Outcomes: how fresh perspectives can solve complex diseases

Developing optimal scientific solutions

Whether it is curing cancer or reversing the threat of climate change, the world’s most complex problems are reliant on scientific solutions. 

Those solutions are often the product of breakthroughs that have been developed in research labs across the globe. While academia and pharma have produced transformative therapies in some diseases, the former is largely optimised for novelty, while the latter prioritises speed to market. Neither of these mechanisms is optimised for delivering curative therapies: Deep Science Ventures (DSV) believes in an alternative approach, capable of delivering ideas that are unlikely to emerge via the traditional routes. 

At DSV, we combine available scientific knowledge with founder-type scientists into high-impact ventures. We take a solution-pull approach to solving the world’s largest problems, starting with the desired outcome for an area and determining the optimal solution to that state; one that is agnostic to the technology required to deliver it. We do not do this alone - we collaborate with some of the world’s leading institutions, corporates and charities.

The importance of partnerships

In our methodology of venture creation, partners are crucial, providing both tangible in-kind benefits such as lab space but also deep technical expertise, beyond what might be available in literature. As will be discussed later, this is critical to our process of venture creation.

The venture creation process starts with identifying a neglected area and the ideal outcome for that space. Examples might include soil regeneration, carbon neutral fuels or treating immunotherapy-resistant cancers. Then, having identified the optimal partner, we initiate a process we call ‘Scoping’, driven in the early stages of our partnerships by members of DSV’s core team. This entails a rigorous first-principles driven, in-depth analysis of an entire disease landscape from many angles, including angles that partners may not have previously considered. Through this phase, we gain conviction in the potential of DSV’s outcome-first methodology to generate new approaches in the disease area, and gain an understanding of the optimal skill set required to get there. 

We next recruit a Founding Analyst, a highly-technical, entrepreneurial domain expert, who will eventually become a Founder of the new venture. With support from the DSV team (100% of our pharma team have a PhD or founding experience), the Founding Analyst will use DSV’s proprietary knowledge-management technology to create a detailed map of the existing technological space, using published research and interviews with an extensive network of experts. Given our partners’ depth of subject-matter expertise, we are able to leverage our methodology and software to convert this combined knowledge into a range of novel potential approaches, which can be evaluated against the desired outcome. 

From these possible approaches, we identify the optimal solution and the other individuals required to form the founding team. Once complete, DSV together with our partner invests pre-seed finance and the company spins-out, confident that they have rigorously assessed the technological and commercial milestones required to validate their concept and scale the business. Many of our partners then continue to work with those teams, whether that is through additional investment or providing facilities like lab space.

Having now created 35 companies and built partnerships with leading organisations such as Cancer Research UK, the Grantham Foundation, Anglo American, AbbVie and CRUSA, our portfolio companies are thriving, receiving follow-on funding rounds from leading investors, and winning major awards on the international stage.

Our partnership with the Children’s Tumor Foundation

An example of a recent partnership at DSV is with the Children’s Tumor Foundation (CTF),  the largest global philanthropic funder of all forms of neurofibromatosis (NF). Obsessed with getting efficacious, tolerable treatments to patients quickly, CTF  funds research into NF, and ensures that discoveries are translated into clinical benefit, while  providing patient support and public education. 

Neurofibromatosis is an area of interest for DSV due to its largely unmet clinical need. NF does not have one individual cause - it is a set of devastating, progressive, rare diseases caused by genetic mutations that lead to tumours forming on nerve tissue. It is a very challenging therapeutic space, complicated by a vast amount of clinical heterogeneity and a limited amount of historical research. 

The term NF represents a family of distinct disorders: NF1 (about 90% of cases), NF2 and Schwannomatosis. These disorders are debilitating to patients. Collectively, they cause tumours on nerves, and depending on the location of the tumours,  they can cause blindness, deafness, and debilitating pain, just to name a few devastating effects. Moreover, NF1 patients may suffer bone and musculoskeletal defects, chronic pain, and cognitive problems. The associated healthcare costs are high, as patients often require complex, life-long, multi-specialist care. 

Although the MEK inhibitor selumetinib (Koselugo) has been approved to treat a subset of NF1 tumours, and often slows or sometimes reverses tumour growth, many patients don’t respond to treatment or experience a range of side effects. Even in responding patients, tumour regression is not complete.

A first-principles approach to neurofibromatosis

In the first months of our partnership with CTF, Anís Gammage, a Senior Associate in Pharma at DSV, collaborated with CTF to scope the NF field to identify the key constraints and bottlenecks holding back progress in NF therapeutics. While Anís is not a specialist in NF, he is a PhD-trained cancer immunologist and computational biologist, and like the rest of the DSV team, has broad expertise, and experience applying our methods and tools to other fields of interest.  

Anís started by taking a first-principles approach to the field, using various analytical tools and publicly available data, as well as talking to subject matter experts introduced by CTF. DSV’s scoping methodology has already allowed him to connect the dots in new ways, and to gain novel insights by assessing the NF space from orthogonal perspectives. This has given rise to new hypotheses around disease biology, such as that Schwannomatosis might be driven by a protein that hadn’t been investigated in this context before, and that a specific type of immune cell could be important in NF tumours. In total, in-house scoping has produced more than 20 ideas for outcomes-focused research proposals, and 4 potentially ‘venturable’ areas, where DSV has generated ideas for completely novel approaches that have no precedence in NF to date, but strong clinical and technical precedence elsewhere. These ideas span from curative approaches, like novel gene therapy vectors and tumour immunotherapy strategies, to disease-modifying approaches and enabling technologies.

“The approval of selumetinib has led to increased interest by pharma and the biotech sector in NF. CTF is excited to work with DSV to assess the investment options of the NF disease space and we see our partnership with DSV as instrumental to our future investments. During the first phase, the DSV team’s skillset in identifying venturable, and even novel, innovative research opportunities combined with CTF’s knowledge of NF and the NF community has been key to success, and we are looking forward to taking the next steps in our partnership”. Annette Bakker, President of Children’s Tumor Foundation. 

Our partnership with the Cystic Fibrosis Foundation

NF is not the only challenging rare disease that DSV is tackling. In 2021 we established a partnership with the Cystic Fibrosis Foundation, to develop new curative approaches for cystic fibrosis (CF). The Cystic Fibrosis Foundation is the world’s leader in the search for a cure for CF, funding more research into the disease than any other organisation and having played a role in nearly every CF drug available today. 

CF is a rare, inherited disease, which tends to worsen over time and can often lead to fatal complications. Over 90% of CF patients die from lung-related complications and, as a result, the focus on CF has primarily been as a lung disease, with most research funding aimed towards lung biology.

CF is not restricted to the lungs. It is caused by mutations in CFTR, an ion channel, that usually transports water and chloride ions in and out of cells. The mutations  give rise to a CFTR protein that does not function properly, because it’s misfolded, shortened, or doesn’t work effectively when it gets to the membrane.

This mutated protein is present throughout the whole body and whilst causing the disruptive build-up of thick mucus found in the lung, it also causes significant symptoms in numerous other tissues including the pancreas, gastrointestinal tract and in immune cell function. While recent advancements in modulator therapies have made cystic fibrosis manageable for many people, there are still thousands globally who still suffer from this debilitating disease. 

A first principles approach to Cystic Fibrosis

To treat the underlying cause of CF, we believe that a multi-organ, systemic approach to cystic fibrosis research and drug development is needed in order to generate curative therapeutic strategies. The ambition of DSV, together with CFF, is to design a new gene therapy that can correct or replace mutated CFTR, not just in the lung, but in multiple affected tissues throughout the body. To do that, together with Founding Analyst Jey Jeyakumar, we are exploring different delivery strategies that have been shown to access these hard-to-reach tissues and re-engineering them to overcome the issues specific to CF.

After a few months of scoping, working alongside DSV Associate Megan Cully, Jey recently presented his intended approach to a panel of CFF staff. They concluded that systematically taking apart and addressing the constraints and challenges presented by the existing CF landscape had led Jey to a therapeutic concept that, if validated experimentally, would represent the first systemic multi-tissue gene therapy for CF. 

“Cystic fibrosis affects many organs, and a systemic genetic therapy would enable us to address complications beyond the lungs. Deep Science Ventures’ unique process has helped us to better understand the challenges that have prevented clinical success in the past as well as what a successful systemic approach might look like in the future.” Kara Foshay, Sr. Director Genetic Therapy Programs, Cystic Fibrosis Foundation.

CFF and DSV have begun recruiting a founder for this approach, as the concept for the new venture is further developed towards spin-out readiness - more details on the role description can be found here.

Different challenges, shared outcomes

Neurofibromatosis and cystic fibrosis share important commonalities: they are both common genetic diseases, incurring devastating consequences for patients, at enormous cost to healthcare systems. It is clear from the current state of patient outcomes, that there is substantial unmet need and curative potential yet to be realised. However, there are also significant differences, most markedly in the volume, depth and funding of research that has been undertaken. This divergence translates into a difference in the depth of disease characterization:

An extensive range of technological approaches have been trialled clinically and pre-clinically for CF, by both leading institutions such as the Cystic Fibrosis Foundation and established pharma companies such as Vertex. With NF, despite a greater prevalence, there has been significantly less funding and commercial interest, leading to a more modest research base  – and a complex pathophysiology that remains incompletely understood.

Yet despite these differences outlined above, each disease benefits from the DSV methodology in different ways: it is adaptable and applicable to diverse scenarios, in rare disease and beyond. In the case of CF and NF, these efforts are already beginning to bear fruit, and we are eager to replicate these successes for other disease areas in future.

Future areas of interest

We are always interested in partnering with forward-thinking, innovative corporates and institutions. Whether in areas where we already have substantial conviction, such as cardiovascular disease, female health and neurodegeneration, or in entirely new fields in which potential partners wish to deliver impact, we are committed to using our outcomes-focused methodology to create transformative therapies in as many unsolved diseases as possible. 

If you are interested in partnering with us, or would like more information on our ongoing venture builds in neurofibromatosis and cystic fibrosis, please email Laura Fletcher, Head of Business Development and Strategic Partnerships - Pharma .