The Blue Box

1 in 8 women will have Breast cancer (BC) at least once, it being the most commonly diagnosed cancer among women worldwide. Shockingly, although BC is one of the most treatable cancers, it is the most deadly cancer in women. This is not because of a lack of treatment options but a lack of accessibility to early-stage diagnostics. Indeed, of all 385M women in Europe, only 130M, (34%) take a mammogram biannually. Of all 255M women who do not get tested, 81% want to, but do not have access to it. This is because the mammogram does not provide clear visualization of small tumors in young women, who have dense breast tissue. Hence, most EU healthcare systems only invite women aged 50-69 to mammogram-based screenings, but 27% of BCs will happen to young women outside screening age.

This is why we have built The Blue Box. When used with young women (<50), our technology is more accurate (78.57% vs 70.40%) and sensitive (83.33% vs 56.10%) than the mammogram. We will provide women aged 20-49 with a reliable and accessible tool to prevent BC. 

Most current methods for breast cancer screening are based on image-based technologies, which do not provide clear visualization of small tumors in young women, who have dense breasts. This is why most European HC systems only invite women aged 45-69 or 50-69 to mammogram-based screenings. As a result, women aged 20-49 cannot get easily tested for breast cancer because existing solutions are unreliable. However, they want to. Additionally, ~1/3 of BC happen in this age range. At The Blue Box, we have built a radiation-free, pain-free, low-cost, easy-to-operate device to detect breast cancer in urine with a sensitivity of 83%, accuracy of 79%, and specificity of 75%. 

The Blue Box is a medical device for breast cancer testing, just by introducing a urine sample in a box. It contains 9 chemical sensors that are sensitive to certain breast cancer biomarkers. In other words, biomolecules that are only found in one’s metabolism if a person has breast cancer. This is what we call “urine’s fingerprint”. While The Blue Box is reading the urine sample, the user will also introduce personal and health-related data via our app, which, together with urine’s fingerprint will be sent to the cloud, where our AI-based algorithm will process it and reach a diagnosis.

a) Young women 

As detailed above, we're targeting a population that does not currently have reliable means to get breast cancer-tested. However, according to 400+ women interviewed, 80% of your women are concerned about breast cancer and would be willing to take a breast cancer test, even if they need to pay for it.

Unlike the mammogram, our solution can be used for younger women who have denser breast tissue: For young women (<50), it has higher sensitivity (83.33% vs 56.10%) and accuracy (78.40% vs 70.40%) than the mammogram.

b) Women with fibrocystic breasts 

The mammogram often fails to properly identify tumors in women with fibrocystic breasts (breast tissue with healthy lumps). Around 40-60% of women worldwide have fibrocystic breasts. Unlike that, when used with women with fibrocystic breasts, The Blue Box has better accuracy (88.89% vs 32.00%), specificity (100.00% vs 39.90%), and sensitivity (80.00% vs 23.70%) than mammography.

Competitive landscape

We are focusing on something that other teams are missing: Solutions to detect breast cancer don't just neet to be effective, but also suitable for screening.

Breast cancer, though among the most treatable of cancers, remains the most fatal form of cancer in women. The existing screening methods are not without limitations. The lack of screening for younger women is not due to a lack of severity of the issue but rather the inadequacy of current technologies.

The Blue Box is based on the WHO’s “Screening Programs: A Short Guide”, which outlines the requirements that a diagnostics tool should meet to “increase effectiveness, maximize benefits and minimize harm”, according to Wilson & Jungner for WHO. Principles 6, 9 and 10 make reference to technological requirements:

“6.  The test should be acceptable to the population.”

“9.  The cost of case-finding (including a diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.”

“10. Case-finding should be a continuous process and not a “once and for all” project.”

Hence, a BC screening tool should be (1) user-friendly, pain-free and convenient for women; (2) as low-cost as possible; and (3) be part of women’s yearly/biannual routine gynecological checkups.

Here is how we have obtained the data to train, test and validate the results we present above:

Pilot Test 1: Ability to detect advanced breast cancer

We started building the first prototype of The Blue Box at the University of Barcelona in 2018. This first prototype cost 35€. To test it, 90 human urine samples were collected from control subjects and advanced breast cancer patients at Sant Joan University Hospital in Reus, Spain. In 2021, class prediction was achieved with a sensitivity of 75% (nature.com/articles/s41598-022-17795-8)

You can access the article here: nature.com/articles/s41598-022-17795-8 

Pilot Test 2: Ability to detect early-stage breast cancer

Since July 2021, we have been training our algorithm for early-stage breast cancer by running 7 pilots at 7 hospitals: University Hospital La Paz in Madrid (ranked among the 100 best in the world),Dexeus Mujer University Hospital in Barcelona, University Hospital Joan XXIII in Tarragona, Sant Joan de Reus University Hospital, Valls Pius Hospital, Consorci Sanitari de Terrassa and Infanta Sofía Hospital. 

In March 2023, we obtained scientific results that demonstrated that we had reached our target of mammography equivalence. Having reached that point, we shifted our focus from R+D to Industrialization. We have been selected to present a poster with our results at the “Congreso Español de la Mama” (Spanish BC Congress), in Madrid on 26-27 Oct, 2023.

  Our core science:

• Science has long demonstrated the feasibility of detecting BC in urine, but there is no standalone urine biomarker that is univocally indicative of BC. We have trained our AI to find BC based on the presence of a set of biomarkers and the proportionality between their intensities. This is our trade secret.

• Body fluids are typically analysed with GC-MS (Gas Chromatography-Mass Spectrometry), but such a method is unsuitable for screening: It is expensive and requires rained personnel and expensive facilities. By adding a substantial layer of data pre-processing, we can acquire high-quality data with a low-cost, easy-to-use, point-of-care device that is fast, accessible, radiation-free and comfortable. This is protected by our patent.
  

Model: Convolutional Neural Networks. See performance in the graph below.

This March, we reached our performance target of mammogram equivalence with urine-based breast cancer test in a pre-clinical study. We also closed €600k in funding, which we are now investing in finishing the design for manufacturing, scheduled for Q1-2024. We are therefore on track to undergo clinical trials in mid-2024 and enter the market in Q1-2025. 

1 and 5-years time goals

1. To validate, via a clinical trial, that the performance of our test is equivalent or superior than mammography, by 2024

To achieve this, we are conducting a pre-clinical study (N>450) to optimise our AI and data processing algorithms. Our sensitivity is higher and our specificity is almost as good as mammography.

2. To have our technology by CE Mark-approved (cleared to be sold in Europe), by 2024.

To achieve this, we are keeping track of all technical implementations related to product design and documenting all patient risks that we can foresee. This constitutes the "technical documentation", and also includes the findings of the clinical trials. This documentation will be submitted to the a notified body to obtain CE Mark.

3. To have The Blue Box be used in a medical setting in Europe, by 2025. 

To achieve this, we are already communicating our value proposition to the medical community and starting conversations with the 7 hospitals participating in our pre-clinical study. As a result, we have been selected to present our scientific results at the Spanish Breast Cancer conference (Oct 2023) and the Breast Cancer Sympossiium in Texas (Dec 2023). This shows that the market is looking forward to receiving our product.

4. To commercialize our technology outside our first market (Europe) at an affordable price, thus increasing accesisbility and compliance to breast cancer screening programs. A special target will be placed in the US and underserved populations, i.e. rual areas in South America where mammography is not accessibel to all women. By 2028

To achieve this, we are preparing the European Technical Documentation in a way that we ensure compatibility with the FDA. 

5. To add new indications to our pipeline, by 2028.

To achieve this, we will conduct R+D so that The Blue Box can also  diagnose other gynecological cancers, starting with ovarian and endometrial. Because our solution is highly based on software, we should be able to achieve so with minimal HW alterations and considerable data science efforts.

Why is now the right time for The Blue Box?

There already exists enough science to make breast cancer detection from a urine sample possible. However, till today, this can only be performed with expensive and big lab machinery, complex sample handling procedures, and trained personnel. A solution like this cannot be brought to all hospitals and can not be financially accessible to all women. Hence, we have created a low-cost, easy to use and portable device that performs as similarly as possible to the aforementioned lab machinery, and made up for the obvious decrease in robustness by implementing high-level data preprocessing algorithms and a curated classification software. Hence, by being a very problem-oriented and patient-centered solution, our product can be made very accessible, and many lives can be saved.

Future developments

Once we have launched our first DaaS, we will keep advancing our science and train our algorithm to detect other cancer types. After exploring this option with our collaborating hospitals, we noticed an urgent need for new technologies to screen for ovarian, endometrial, cervical, uterine, and vaginal and vulvar cancers. There are currently no non-invasive and accessible tools to do so. Moreover, each year, 71,500 women are diagnosed with, and 26,500 women die from gynecologic cancer. 

Judit (F), co-founder & CEO

Full time. Biomedical Engineering BSc (UB), Embedded and Cyber-Physical Systems MSc (UCI).

Lidia (F), COO

Full time. Building Engineering  BSc, PhD.

Joan (M), CProductO

Part time. Biomedical Engineering BSc (UB), Technological Innovation in Health MSc (European Institute of Technology). Previous experience as co-founder and CTO.

Celia (F), CDataO

Full time. Biochemistry BSc, Omics Data Analysis MSc. PhD on cancer detection in buifluids (UB)

Marisa (F), QA/RA Manager

Part time. 20 years of experience leading 20+ developments of in-vitro diagnostics.

6 years of combined research at the University of Barcelona and the University of California Irvine led to the identification of relevant biomarkers and the optimal sample processing method for BC identification. The first part of the research was Judit's bachelor thesis (2018), and master thesis (2020). Celia's PhD thesis (2019-2023) was the second part of the research.

The company was founded in California in 2020 and in Spain in 2021. Joan, Lidia, Celia and Marisa joined the team in 2021, 2022, 2023, 2023 respectively.

Our leadership team continuously strives to auto-evaluate themselves and collect feedback from their peers to ensure that The Blue Box Biomedical Solutions is a place where diversity is valued and celebrated. In fact, our team includes women taking up technical roles, as well as members of the LGTBI+ community.

We will have two revenue streams:

• We'll charge clinics a monthly subscription to rent our HW. 

• We’ll distribute our product as a SaaS (Software as a Service): We’ll charge a fee per SW run, i.e. per each BC test

In turn, healthcare facilities will sell Blue Box tests to women as a DaaS (Diagnostics-as-a-Service). A clinic running 30 tests/day would get a €5,164.45 monthly revenue if selling the tests at our RRP of €47.

We estimate we will be able to mass-produce our hardware for €700, a minimal cost in comparison to the order of magnitude of our software-related revenue streams. Indeed, our SW-based business model yields >75% gross margins and scalability: In 2029, we'll have 340M€ in revenue (320M from SW, and 20M from HW). As we grow, we'll shift our revenue focus into SW - in 2033, we'll have 1B€ in revenue (1B from SW, and 70M from HW).

Ongoing pilots at 7 hospitals

In Europe, BC is the most frequent cancer in women. In Spain, BC is the most frequent cancer, responsible for >25% of all cancers. We are currently piloting with 7 Spanish hospitals. We are creating relations with heads of gynecology which have an influence on the purchasing department of hospitals. 

We are currently funding our project thanks to €500k received in private funding (investment) and €1M in awards from governments and non-profits. However, we plan on becoming profitable 6-9 months after market launch. Having reached this point, we will reinvest our profits in R+D to keep improving our performance (further training our AI), and adding more centers to our pipeline. We describe our future market below.

The EU market 

Of all 255M women in Europe who do not get tested, 81% want to, but do not have access to it. In other words, 120M European women aged 20-50 are right now looking for a solution that the system cannot deliver. They are our 1st customer segment. 

The US market

Inefficient breast cancer screening in the US healthcare system is currently a $34B problem. The global breast cancer screening market is as big as 40B$, and 50% of this market is taken up by image-based technologies. We’ll provide a solution to tackle this problem by first focusing on a $95M sub-market. We envision young women (70M women in the US) getting screened in 30 minutes while shopping at CVS’ MinuteClinics, Walmart Health or Walgreens.

Revenue Streams

We are addressing these markets:

• 2025: Spain Pilot launch, first market launch to find product-market fit

• 2025: European launch, market roll-out, adapting our model country by country

• 2027: US launch, a big market where to scale up our business

After finding product-market fit in Spain, we will expand in Europe. Germany is a great market to launch a device like The Blue Box, since 89% of the population seeks general medical care yearly, and it has cancer centers and women's clinics together in shared facilities.