Menopause and neuroscience.

70% of women experience neurological symptoms during the menopausal transition, and while historically menopause was associated only with the ovaries, it’s now understood that symptoms such as hot flashes, forgetfulness, mood changes, and insomnia are all neurological symptoms, writes The Guardian.

While very few brain studies look at menopause, interest in the topic has been surging lately.

The 2021 study led by Lisa Mosconi, the largest examination of the menopausal brain to date, showed substantial differences in brain structure across the menopause stages. Critically, many of these changes are temporary, and the brain tries to compensate for these changes through increased blood flow and energy production.

Other studies found an association between frequent hot flashes and an increased likelihood of having Alzheimer’s disease biomarkers and that the first signs of the brain disorder can appear at about the same time women start menopause, suggesting the hormonal event might have implications for disease risk.

There was a bunch of news around menopause, so I’m listing them right here as well:

• On February 28th, researchers from University College London pooled the data from 22 studies and concluded that talking therapies such as CBT and mindfulness-based interventions (MBI) could help with physical menopause symptoms, like hot flashes.
• March 5th, It’s time to stop treating menopause like a disease, according to Lancet: The article calls for a reframing of menopause and a management approach that is not simply focused on medical interventions that relieve symptoms.
• On March 22nd, the recent Nature study on whales may show the evolutionary nature of menopause (which presents itself in very few biological species). Just as in humans, menopause in toothed whales evolved by selection to increase their total lifespan without also extending their reproductive lifespan. This could provide insights for our understanding of the evolution of menopause in general.

While the studies have their limitations, it’s important to see the surge of research interest around the topic.

PMS

On March 5th, Flo Health Inc. shared the results of their RCT demonstrating the effectiveness of the Flo app in improving PMS symptom management. In 3 months, the use of Flo significantly reduced symptom burden and decreased the number of absent days from work (the study results were accepted for publication at JMIR).

Addressing PMS has the potential to contribute $115 billion to the global economy. But, as of 2015, the number of scientific studies about erectile dysfunction exceeded that of premenstrual syndrome by 5x.

A reminder: in January 2024, Flo published their research in Nature NPJ Mental Health, exploring the effects of acute stress on pain perception among women during the Russia-Ukraine conflict (based on de-identified data from over 88k Flo users in Ukraine). Higher stress levels were linked to lower pain sensitivity. See here for more.

IUD for fertility

This month, I was fortunate to visit the Montpellier regional development agency, AD’OCC Invest in Occitanie, thanks to Angélique CACHEUX, and read and learn more about the local startup scene, including its digital health potential. In a local magazine (practicing my French), I noticed an article about Womed, a startup developing the first fertility-oriented IUD (intrauterine device). The device is CE-marked and, in 2021, has already demonstrated its safety and efficiency in a trial of 23 patients.

Apparently, on March 7, 2023, Womed announced that the results of the PREG2 clinical trial demonstrated Womed Leaf® is effective in the management of severe and moderate intrauterine adhesions (IUAs), the primary mechanical cause of female infertility. At the 6-week follow-up visit, women who received Womed Leaf were 2.4 times more likely to have no adhesion than those in the control group.

Depression and cardiovascular disease

On March 12th, women with depression might face a higher cardiovascular disease risk than men:the study published in JACC: Asia tracked and reviewed medical claims between 2005 and 2022, analyzing more than 4 million patients. The results suggest that the hazard ratio of a depression diagnosis leading to CVD was 1.39 in men and 1.64 in women. While the study has some limitations, it raises the important point of treating patients as the whole person in the world of sub-specialties and considering connections between mental and physical health.

Latest research in endometriosis

Oxford University scientists conducted the largest genetic study of endometriosis to date, published in Nature Genetics (using the data of over 60,000 individuals diagnosed with endometriosis and more than 700,000 control subjects). The study revealed 42 genetic regions that are significantly associated with the disease, many of which are related to pain perception.

In 2023, researchers from Cedars Sinai used single-cell genomics technology to map out the molecular profile of endometriosis, providing detail on the condition’s complex cellular makeup (published in Nature Genetics), using nearly 400,000 cells from a total of 21 affected or healthy individuals. The study can be a game changer for identifying potential therapeutic targets at a cellular level; it could enhance treatment outcomes and reduce disease recurrence.

Other studies investigated connections between endometriosis, IBS, and the gut microbiome, as well as its association with mental health conditions. While past research suggested these mental health issues were merely byproducts of chronic pain, the study reveals their distinct genetic underpinnings, expanding our understanding of endometriosis beyond its reproductive implications.

A reminder: in February 2024, we saw the first promising results from the clinical trial of the first non-hormonal, non-surgical treatment for endometriosis (dichloroacetate) in Scotland. If the trial is successful, the drug (the first in 40 years!) could be on the market within 5-7 years.

March 19th, In the US, Biden signs an executive order to expand and improve how the US federal government funds health research about women, calling for an investment of $12 billion in new funding for women’s health research.

On March 19th, Bloomer Tech from Cambridge is launching a clinical trial for their smart bra that tracks heart health. The bra, which originated a decade ago at MIT, collects data about women’s cardiovascular system, hormones, and metabolism, showing the results on an app. The device underwent a feasibility study in 2018 and other tests with humans before Bloomer Tech prepared for the latest clinical trial.

Smart bras might be a great twist in the medical device industry; check out IcosaMed from Switzerland, a smart bra for breast cancer monitoring. IcosaMed’s technology emits ultrasound waves to perform echography scans for potentially cancerous cells.

March 21st, An AI breast screening solution called Mia (CE Mark IIa) helped doctors find an additional 12% more cancers than in routine practice during the collaboration between Kheiron Medical Technologies, NHS Grampian, and the University of Aberdeen (as part of a study with 10,889 patients). The augmented AI workflow also showed a decrease in women recalled unnecessarily for further assessment and modeled a workload reduction of up to 30%.

About 20% of women with breast cancer have tumors that are missed by mammogram screening, which is why many countries mandate that two radiologists should read every mammogram.

Overall, it seems like McKinsey coined the term ‘closing the women’s health gap’ with their report on the state of women’s health, released this January. There’s been a handful of publications and interviews repeatedly referring to the report and the ‘gap term’, or citing the studies mentioned in this report. I hope that this awareness surge will greatly contribute and lead to concrete developments in the mid-term.

More from Anastasiya Markvarde:

A Stanford University School of Medicine-led study shows why women are at greater risk of autoimmune disease and why it has gone unnoticed for a long time in research.

Autoimmune diseases disproportionately affect women, with 4 out of 5 patients being female. The ratio for lupus is 9 women to 1 man, and for Sjogren’s syndrome, it’s 19 to 1. A molecule produced by one X chromosome in every female cell can generate antibodies to a woman’s own tissues. In female mammals, cells shut down one or both X chromosomes early in development to avoid overproducing certain proteins, which can lead to autoimmune disorders. This process, called X-chromosome inactivation, is controlled by a molecule called Xist. However, traditional testing methods, which use male cell lines lacking Xist, fail to identify anti-Xist complex antibodies in female patients, contributing to autoimmune susceptibility.

The first promising results from the clinical trial of the first non-hormonal, non-surgical treatment for endometriosis started in 2023 in Scotland, plus my deep dive into the endometriosis area.

A clinical trial for the first non-hormonal, non-surgical treatment for endometriosis showed promising results. The drug, dichloroacetate (DCA), reduces high levels of lactate, offering relief to patients. With larger trials underway, the drug could hit the market in 5-7 years. Meanwhile, innovations like Hera Biotech’s non-invasive test and Ziwig Biotech’s saliva test offer hope for a quicker diagnosis. Startups like Imagendo and Syrona Health also provide digital solutions for tracking symptoms and accessing information. More digital therapies are needed to offer immediate relief to endometriosis patients.

The first new endometriosis treatment in 13 years, Ryeqo by Gedeon Richter Australia, has been approved by Australia’s drug regulator, even though it won’t receive government subsidies.

Preliminary results from a 3-decade Finnish study show increased disease among women: almost 50% of women born in 1986 and followed since developed some kind of chronic disease, despite their young age.

The Swedish study finds that menopause is getting worse: the prevalence of symptoms increased from 24% to 35% over 1 generation, with no straightforward explanation to be found yet.

With 60% of women dropping out of their healthcare journey in France, Paris-based Sorella Care aims to transform women’s patient journeys with their hybrid clinics. Sorella announced a €5 million round just one year after launching its first multidisciplinary health clinic.

More from Anastasiya Markvarde:

Deeptech investments were one of the most resilient categories in 2023. However, did you know that 95% of patents in Europe remain inactive and never find their way into companies?

I have been working with and reading a lot about deep tech lately, and there is a lot of optimism in this category. For example, amidst an overall funding decrease in 2023, deeptech startups in Europe are estimated to get almost the same amount of funding in 2023 as in 2022 ($17.6 billion vs. $18.9 billion).
Together with being among the most resilient, it’s also the largest category in VC, followed by energy and tech. 
However, one figure that got really stuck in my mind is that 95% (!) of Europe’s patents never find their way into companies and products (Deep Tech report by Dealroom.co and Walden Catalyst Ventures). I feel like this is something we need to address with strong partnerships between universities, industry, hospitals, and the public sector working together.

A busy start of 2024 in digital health with several big partnerships between pharma and digital health or therapeutic companies (Vicore Pharma AB & Alex Therapeutics, Aptar Digital Health & Gerresheimer, MENARINI Group & Insilico Medicine) plus FDA approval of DTx for schizophrenia by Click Therapeutics, Inc. and Boehringer Ingelheim, and more.

EVERSANA shares an expert article on patient adherence that delves into the main causes of poor adherence rates across the patient journey and the sophisticated solutions necessary to counteract this widespread issue. It is estimated that up to 50% of treatment failures can be attributed to nonadherence, resulting in 25% of hospitalizations and approximately 125,000 deaths annually in the United States (U.S.), costing an estimated $100-300 billion in avoidable healthcare expenses each year.

2023 in digital health and 2024 outlook: a summary of reports by PitchBook, HSBC, and also Rock Health (For the full version, go to the newsletter of Nicola Mattina here.)

Both reports approach the healthcare market in 2023 from different perspectives: Pitchbook has more statistics on PE/gglobal VC investments, IPOs, deals in biopharma, and some specific trends like AI or surgical robots, while the HSBC Report offers a bigger investment and financial deep dive by category or therapeutic area. 
I was curious to look at both at the same time, as combined, they offer a great overview of the year in health technology.
Some insights from Pitchbook:
Healthcare’s share of global private equity (PE) and venture capital (VC) deals is declining due to the pandemic’s impact. After peaking in 2020 at 18.4%, it dropped to 16.5% in 2023, with further decreases projected for 2024. Digital health exits are expected to rise in 2024, but challenges persist, including limited investor demand for unprofitable IPOs. Biopharma startups will require stronger clinical validation, like successful phase 2 trials, before pursuing IPOs. Generative AI is anticipated to disrupt care coordination, reflecting a shift toward AI solutions in healthcare.

Some insights from HSBC:
In 2023, the healthcare market stabilized, but new investor rates dropped by 28%. Despite this, the top deals still saw valuation increases. However, about 50% of healthcare financings were add-on or insider rounds, posing challenges for 2024 fundraising. VC investment in healthcare decreased by 28% from 2022 and 53% from 2021. There’s a shift towards focusing on fundamentals and later-stage clinical exits in health tech investments.

France is taking over digital health in Europe. Here is another exciting reading by Tara Donnelly.

France stood out among Europe’s top 10 tech markets in 2023, with only Italy matching its increase in VC fund closures. French VCs closed 29 new funds, raising €4.7 billion, up from €4.4 billion in 2022. The growth is credited to France’s expanding VC ecosystem, supported by government and Bpifrance funding. Bpifrance’s commitment to funds increased to €1.6 billion in 2022, supporting various programs from accelerators to late-stage growth equity. French VCs announced 11 new fundraisings in Q4 2023, including the Sofinnova Partners Digital Medicine fund (€190 million). France ranked 6th globally in health-sciences research output, and Assistance Publique-Hôpitaux de Paris made the Nature Index global top 15 for research output. Despite challenges, France is emerging as a promising market for VC and digital health.

An AI startup called Anthropic, an OpenAI competitor backed by Amazon, co-authored a study on deceptive behavior in AI models. AI models learn quickly how to be deceptive, which cannot be easily reversed. Moreover, safety training techniques not only won’t reverse deception but could make it worse and reinforce it.

Enough is being posted on AI and how it’s undoubtedly going to transform all industries, including healthcare, but I found this paper curious to share.
Researchers at AI startup Anthropic, an OpenAI competitor backed by Amazon, co-authored a study on deceptive behavior in AI models (10 January 2024). They found that AI models learn very quickly how to be deceptive, which cannot be easily reversed. Moreover, safety training techniques not only won’t reverse deception but could make it worse and reinforce it.

What’s happening with VR investments and the new VR device by the Finnish company Varjo?

Varjo‘s latest XR-4 device showcases exceptional quality and resolution, catering to industries like defense, automotive, space, and healthcare for training purposes. While XR and VR are finding applications in healthcare, the industry faces market challenges.
Crunchbase‘s recent report on metaverse, VR, and AR investments highlights stability in 2022, with $5.73 billion invested across 576 transactions, akin to 2021 figures. However, 2023 witnessed a significant downturn, with investments plummeting to $1.97 billion across 226 transactions. Notably, there were no US rounds exceeding $100 million in this sector.
The decline might echo the 2023 digital health funding drop, signaling a shift towards results and adoption over hype. This trend could lead to industry consolidation, with fewer but stronger players focused on delivering tangible value. The future trajectory remains to be seen.

7 Open Innovation Trends as the Industry Turns 20+ Years.

The open innovation industry is now 20+ years old, which means it’s gone through stages of early development, strong growth, and big hype and is now recalibrating and reaching maturity.
Key trends in 2024 include shifting focus from ‘why’ to tangible results, moving towards industry-specific verticals, focusing on education and change management, gaining momentum in ecosystem engagement, emerging corporate innovation models, smaller players participating, and opportunities for experts in complex industries.

“Although women account for 70% of chronic pain patients, 80% of pain medication has been tested only on men or male mice.”
2023 Women’s Health Updates Summary: new FDA approvals, government initiatives in Canada and the UK, and, of course, the McKinsey & Company report and Kearney and FemTechnology present an open letter in Davos.

In Canada, British Columbia launches a pioneering self-screening cervical cancer plan. Qvin secures FDA approval for the first menstrual blood health testing pad. Flo Health Inc. presents groundbreaking research on acute stress’s impact on pain perception in women during the Russia-Ukraine conflict, published in Nature NPJ Mental Health.
Women’s health dominates the Davos summit, according to McKinsey & Company’s report. Kearney and the FemTechnology Summit collaborate on an open letter and a $55 million initiative. Despite a challenging investment market, Midi Health, a virtual menopause care startup, raised $60 million, just four months after their last funding round

Ophthalmology is a niche field, and not so much is published around innovation in the industry, so let’s take a look.

The French Tilak Healthcare has announced positive results from its TIL002 study using the OdySight® app (a prescription-only CE-marked medical device), which allows patients with retinal diseases to monitor their vision themselves. 
The prospective multi-center study showed a high level of convergence between at-home evaluations of visual acuity measured with OdySight® and standard methods used during consultations, showing the solution’s reliability. 
The numbers: the study looked at 58 patients and 105 eyes and took place over 1.5 years across 3 centers in France.

“As interest in AI calms down, make sure not to overlook quantum.” State of Quantum 2024: Report Takeaways. Healthcare is one of the three industries expected to be influenced by quantum technologies.

IQM Quantum Computers, with OpenOcean, Lakestar, and TQI, reported on quantum tech. The top impacted sectors are healthcare, cybersecurity, and finance. Quantum gets <1% of VC funding and faces challenges in finding small-scale use cases with limited budgets. It enhances AI, and in 2024, more organizations are expected to become ‘quantum ready’ with a focus on immediate value through hybrid systems. Challenges include high costs and security concerns. In healthcare, quantum could expedite therapeutic discovery, improve diagnostics, enable personalized medicine, and enhance data-driven health policy planning.

Original post published on LinkedIn Pulse

Historically, women were excluded from drug trials due to concerns about potential fetal harm and economic factors related to data collection and side effect reporting. Even today, women experience more drug-related adverse events than men. Until recently, women’s disorders were dismissed as ‘hysteria’, perpetuating harmful stereotypes.
Diseases like migraines and endometriosis receive disproportionately low funding compared to their burden. Heart disease symptoms in women are often misdiagnosed, leading to undertreatment.
The Lancet highlighted long-term childbirth consequences affecting millions of women, exacerbated by a lack of high-quality guidelines, especially in low- and middle-income countries.
HIV trials also show underrepresentation of women. While recognition of these gaps is growing, concerted efforts are needed to ensure women’s inclusion in clinical research and advance femtech initiatives. Reflecting on historical facts can guide meaningful progress in women’s health research.

I feel like there is so much going on in the femtech space that I can’t possibly wait another 7 days in January with the risk of never finishing my article.

As always, I would like to share a quick resume of what is going on in the women’s health industry. The idea is to give an overview of the landscape, put together a condensed summary, and highlight the main points of what has happened in the space. The news is connected to new care programs, digital therapies, reports, and startup investments.

On January 9th, Canada launches the first self-screening cervical cancer plan in British Columbia.

A province-wide screening in British Columbia will allow women to order a quick, easy, and highly accurate test kit to use at home and will allow them to access a network of highly trained and compassionate medical professionals who will support those identified as being at higher risk. (Also, on January 19, the Femtech Canada initiative launches to support women’s health ventures.)

Also biotech research company Qvin announced the first ever FDA approval for a pad for menstrual blood health testing.

The Q-pad offers a less invasive and more accessible alternative to a blood test and, more importantly, makes a very important step to use menstrual blood (historically neglected in research) for healthcare screening purposes.

On January 10th, Flo publishes groundbreaking research in Nature NPJ Mental Health, exploring the effects of acute stress on pain perception among women during the Russia-Ukraine conflict (based on de-identified data from over 88k Flo users in Ukraine).

Higher stress levels were linked to lower pain sensitivity. This discovery is the first documented real-life example of extreme stress being connected to reduced pain sensitivity, ‘or’stress-induced analgesia’, and the first study to explore SIA in a real-world setting.

On January 17th, McKinsey releases a fundamental report on the $1 trillion opportunity to close the women’s health gap.

The report highlights that women spend 25% more time in poor health compared to men, with 64% of interventions resulting in disadvantages due to access issues or lower effectiveness. Women’s health research often overlooks diseases with higher mortality rates and lacks sex- and gender-specific data. Women also face delays in diagnosis, with studies showing it takes 2.5 more years for cancer and 4.5 more years for diabetes. Access to care is also disparate, with women in Switzerland paying 37% more than men. Investors are encouraged to support women-centric research and financing models.

As a response to the report, a new Global Alliance for Women’s Health initiative has been launched, with $55 million allocated to women’s health.

Supported by 42 organizations and pledging $55 million, the alliance responds to a report highlighting the underestimated health burdens faced by women. Investing in women’s health could yield up to $1 trillion annually by 2040, improving outcomes for over 3.9 billion people globally.
The alliance focuses on financing, science and innovation, and agenda-setting, with commitments from governments, philanthropies, and pharmaceutical companies.
Key commitments include $25 million from Tower Capital Group and $30 million from Rotary International for maternal and child health initiatives in several countries.

On January 18th, Kearney and FemTechnology presented their open letter and report for change on redesigning healthcare with women in mind in Davos.

Although women account for 70% of chronic pain patients, (yet of) pain medication has been tested only on men or male mice. On average, women wait 4 years longer than men to receive a diagnosis for the same disease.

The letter encourages action by tackling the public health agenda, building women-centric care pathways, and accelerating investment.

On January 17th, the UK health secretary announced new women’s health priorities for 2024.

Top priorities under the Women’s Health Strategy in 2024 include menstrual problems and menopause, maternity care, and birth trauma support. £50 million for research to tackle maternity disparities through the NIHR research inclusion strategy.

The priorities result from input from healthcare professionals and the public. The strategy aims to break historical barriers, reduce disparities, and enhance overall women’s health, with a renewed focus on menstrual conditions, women’s health research, and support for abuse victims. The government also reappointed Professor Dame Lesley Regan as Women’s Health Ambassador for England, emphasizing the ambition to provide world-class treatment and improve healthcare outcomes for women.

On January 19th, Midi, a startup offering virtual menopause care, raised $60 million in the tough investment market just 4 months after their last founding round.

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It’s promising that the historical gap and disregard for women’s health are now recognized, and efforts are being made to address them. I do hope we will start seeing the results in the coming years and decades. It’s quite obvious that we need to involve more women in trials and invest more in women’s technology, but what about small first steps that could have an immediate effect?

I thought of a basic blood test. As a rule, it doesn’t carry information on a woman’s day of cycle, only when the tested values are directly linked to women’s hormones. However, the menstrual cycle can influence various biomarkers in a complete blood count. For example, the leukocyte count increases in the second phase of the cycle. Other parameters that can significantly fluctuate across the cycle are iron, lipids, thyroid hormones, insulin, blood glucose, and even vitamin D.

It could cost little or nothing to include the information on the day of the cycle in each blood test and start yielding results already today, even before we can leverage the collected data for research purposes. Thoughts?

In anticipation of Frontiers Health Global Conference (October 20-21^st, in Milan & online), we spoke to Tanja Dowe, CEO of Debiopharm Innovation Fund, about a white paper the Fund is about to release: Surviving and Thriving in a Tough Market: Advice for Start-Ups.

In their third consecutive year as a conference partner, Debiopharm will curate a session  where they will present the findings of the white paper and share more comments and personal perspectives of entrepreneurs and startups on the topic.

Tanja, first of all, do you think that most of the startups in the industry have clearly realized that the market conditions have changed?

I think that everyone has realized that times have changed and we see a lot of writeups in the media about the investment amounts that are decreasing or increasing depending on the source, stage of the companies and so on. Many opinions are out there on what you should think about the markets or how you ensure that you survive through these times. Which means that, indeed, the entrepreneurs acknowledge they are in the middle of the shifts in the environment. But the important question is: have the entrepreneurs adjusted and how have they adjusted?

In our white paper we decided to talk to people who went through the recessions of 2003 and 2008 to get some depth, try to understand if we are going into a full-blown recession that many banks are now forecasting, and what does that mean to entrepreneurs? And how can you find a better way to get through it if you are a startup or a scaleup from the digital health & life sciences industry. During our session at Frontiers Health, we will reveal the summary of the white paper findings.

In a startup-investor relationship during hard times, the responsibility of a startup would be to manage investors’ expectations. What is the responsibility of an investor? How is Debiopharm Innovation Fund supporting the portfolio startups?

One of the first things that you have to do as investor is to adjust your expectations. You have to take a very close look at your portfolio companies one by one. Can they grow as quickly as anticipated? Can they get to profitability as quickly as you expected? And what is the exit market going to look like?

Usually, when we invest in a company, we have an idea of how the company will grow if things go well, when they are going get profitable, when they are going to exit, and so on.

Obviously, in this type of market, we have to revisit our expectations and adjust them. It doesn’t mean that we’re going to be happy with lower IRRs, but we may have to adjust the timelines or think about what can we do to support the companies. For example, we may have to be ready to bridge some of our portfolio companies if their fundraising rounds are coming in the next 6 or 12 months, because it might make sense to postpone the next bigger raise till times get a little bit better. Some adjustments to the business plan might be needed and so on. So we have to be flexible, just like the startup entrepreneurs have to be flexible as well.

Another important thing worth taking into consideration is that a lot of investors are very good at modeling financial performance and growth. But startup life is much more about pivoting, and the best investors can help with that. I think there has to be a balance between listening to startups that are in the field and sticking to strategies and milestones. . If we work together as investors, board members and founders, it’s great, but it really has to be a team. The entrepreneurs have to listen to investors, but investors also have to listen to entrepreneurs.

Is there a place for optimism when adjusting the goals and numbers during a downturn?

I think that especially in such industry as digital health, the fundamentals and the macro trends remain the same. The need to renew healthcare and to bring digitalization into it is not going to go away. The solutions that help bring healthcare costs down might even attract more attention.

Also, we have to admit that pressure forces every one of us to be more creative. I think that startups have the best chances to be creative and to change quickly, compared to big industry players who are having a harder time adjusting to tougher markets.

To know more about the white paper findings and valuable insights for startups, secure your pass to Frontiers Health now and join the Debiopharm’s session, moderated by Tanja’s colleague, Nicolas Stalder, Investment Associate at Debiopharm Innovation Fund, at 11 00 CET on October 21^st!

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About Debiopharm’s strategic digital health fund

As Debiopharm’s strategic corporate fund, the Debiopharm Innovation Fund invests in digital health, smart data, and innovative tech start-ups. Find out more about seeking digital health start-up funding.

In this context, a fundamental role is played by startups and innovators, who develop solutions that are able to respond effectively to the emerging needs of patients, caregivers and healthcare workers. A new initiative is offering valuable support for the growth and development of digital health startups, as well as sparking open innovation inside the healthcare ecosystem. We are talking about VITA Accelerator, the new accelerator of the National Accelerators Network of CDP Venture Capital, set up together with Healthware Group and Danish accelerator Accelerace.

To learn more about the VITA Accelerator, we interviewed Paolo Borella, Managing Partner and Head of Program of VITA, who brings to the initiative more than twenty years of experience in building acceleration and open innovation programs.

What is the objective and focus areas of VITA Accelerator?

VITA is the first Italian accelerator of the National Accelerators Network of CDP Venture Capital, entirely focused on the digital health vertical. The Program aims to support startups with innovative and scalable solutions in digital health and it also represents an important opportunity to strengthen the Italian digital health ecosystem, ensuring that it becomes a point of reference in the international scene.

It is important to underline that we target not only Italian startups, but all companies in the pre-seed or seed phase that intend to open a registered office in Italy. For the first batch we will select up to 10 startups that will have an exclusive opportunity to collaborate with the Innovation Partner Zcube –Zambon Group’s research venture – and with the Corporate Partners Petrone Group and SIFI. The startups will also get access to the network of over 20 Ecosystem Partners, among which Enpam Foundation, FADOI, Panakès Partners, Italian Tech Alliance and Healthware Ventures.

How can a startup access the Program and what are the benefits be for the selected startups?

Our Accelerator will have 1 batch per year over 3 years, and we will be accelerating up to 10 startups per batch. In order to take part in the first cohort of VITA you just need to apply on the website by 12 June 2022.

The first batch will start on July 18 and will last 5 months. Each team will be able to strengthen their business thanks to the lectures, workshops and one-to-one sessions with the best experts in the sector. And, as mentioned before, selected startups will also have the opportunity to work on our Partners’ Innovation Challenges by developing POCs (proof-of-concepts).

As part of the program, the startups will be able to reside at Palazzo Innovazione, the Italian headquarters of Healthware Group in Salerno, and at the OpenZone satellite hub, Zambon campus near Milan (Bresso). Onsite sessions will be combined with the online one sas we believe that the hybrid format offers a good balance between in-person interaction and having time to actually work on the defined goals.

An important factor, that I consider strategic for the startup growth, is being in the midst of exchange of knowledge and experience. I am thinking, for example, of the exchange of know-how between startups and partner companies, but also of the one between mentors and startups and – why not? – also between the teams. These open innovation processes, emerging within the frames of the Program, will stimulate new synergies and collaborations that I hope will continue beyond our Accelerator.

Another great opportunity for all selected startups is the investment of € 110K (of which € 50K in cash) with the possibility of the follow-on investments of up to € 2M. These investments will, in general, will accelerate the digitalization of the health system, that we hope will benefit from the innovative services and products that will be developed.

The first batch will end in November of this year, and everyone is welcome to meet the Partners, the startups and learn about the results achieved at the Demo Day organized on the occasion of the Frontiers Health conference on October 20-21st.

How can VITA Accelerator contribute to the growth of the Italian digital health ecosystem?

For many years I have lived between Italy and Finland, where I have actively contributed to the local startup scene by founding Vertical, a company specialized in open innovation, as well by being active as a mentors and expert in various programs, including Startup Sauna or holding the role of Director of AppCampus, an accelerator funded by Nokia, Microsoft and Aalto University. Finland and Italy are very different countries and undoubtedly the former is known for being among the most innovative hubs in Europe.

However, the Italian ecosystem obviously has a great potential and is capable of attracting not only startups but also international investors. Over the years I have worked in sectors with a high technological impact, but I believe that today the health sector has, more than ever, a strategic importance and this has prompted me to return to Italy and to invest my expertise in VITA Accelerator. Together with CDP Venture Capital, Healthware Group, Accelerace and all the other partners, we will support the most promising companies to ensure that they are ready for the challenges of the market and, at the same time, we will create synergies with the main stakeholders in the sector to give a strong boost to the digital health ecosystem.

Find out more about VITA here www.vitaaccelerator.it and submit your startup by June 12 here

Article originally written in Italian and posted on www.digitalhealthitalia.com by Giovanna D'Urso, Marketing & Communications Manager at Healthware Group.

Digital Therapeutics (DTx) are rapidly gaining momentum and growing in number and quality across all therapeutic areas. In this context, pharma companies are facing the challenge of exploring ways to incorporate software therapeutics in their product portfolios.

While DTx can provide a lot of value for pharma (improve patient outcomes, support existing drugs, create additional revenue streams and allow for greater patient interaction), the real challenge lies in choosing the right ways to incorporate DTx in the business operations of pharma companies.

In May 2021, Plexus Ventures and Healthware Group hosted an insightful webinar on the evolution of pharma-DTx partnership (you can read key takeaways from the webinar here). The topic generated great interest from the audience, therefore the session at Frontiers Health 2021 will be a continuation of this fruitful discussion, diving deeper into exploring the value of DTx for pharma companies.

The session, moderated by Kristin Milburn, Managing Director at Healthware Labs, will include Gabriele Tundo, Partner at Plexus Ventures and Gerry Chillè, Head of Digital Therapeutics at Healthware Group.

About Plexus Ventures

Plexus Ventures, a proud conference partner, supports companies of all sizes and capabilities in achieving their strategic objectives through business development deals and built an international reputation among pharmaceutical and consumer healthcare companies all over the world.

In partnership with Healthware Group, Plexus aims to accelerate collaborative alliances between DTx and pharma companies by leveraging its decades of experience in successfully structuring transactions through a meticulously designed process.

Join Frontiers Health conference on November 11-12th in Milano or online and get a chance to network with Gabriele from Plexus Ventures and many other international health innovators!

Debiopharm is a proud partner of Frontiers Health 2021 conference that will take place in Milan, Italy & virtually on November 11-12^th. As a part of the conference’s program, Debiopharm will curate the session ‘You’ve Got Your Series A Funding – Now What?’ where the speakers will reveal numerous insights into scaling a digital health company in the post-series A phase. The discussion will include both startup and investor perspectives on the topic.

In the anticipation of the session, we asked Tanja about the role of investors in a startup scaling process.

Nowadays, there is a lot of talk about ‘smart money’ from investors, meaning that startups are looking for something beyond just investment, like quality network and other support. What’s your opinion on the role of investors in the startup development path?

It’s true that when startups look for investors, they usually have a certain profile in mind. But we have to acknowledge that money is the first most important factor. Without it, no matter how wonderful advice an investor gives, there is no startup development happening.
If we talk about further support from the investor’s side, I’d point out helping the startup to understand the domain and the market. Many digital health companies come from an intersection of technology and healthcare, and very often at the Series A stage, while the engineering side of the company is well developed, the medical part is still less-shaped and there is no fully comprehensive understanding of market needs. Understanding of market needs also includes a clear vision on who the startup is ultimately serving: pharma companies or health care providers, etc. and investors can add a lot of value here.
Then, investors can contribute a lot with the connections to potential customers, providing access to the type of advisors that intimately know the fields that the startup needs expertise in and guiding the startup in asking the right questions.

And obviously, another important point are good relationships with the next round investors. If a startup is raising Series A, it is beneficial to have an investor that has deep enough pockets to participate in Series B and bring other investors along.

Can you tell us more about how Debiopharm Innovation Fund supports the portfolio companies? What sets you apart from other investors?

My answer to this question consists of two parts. First, our specialty is providing startups with an access to pharma experts from Debiopharm. Depending on whether a startup is selling, for example, to pre-clinical or clinical operations, or to the market access team, we facilitate connection to panels of experts from Debiopharm to help the startup’s team to understand the needs of their clients. The idea is to give them an opportunity to talk with our experts in a relaxed environment and test their ideas before they go and talk to their actual customers. In this way, we help the teams to understand the market dynamics and the pains of the clients they will be interacting with.

To sum up, a warm relationship with Debiopharm’s internal stakeholders and the willingness to help figure out the target market is definitely something we can offer.

Then, the second part is about what sets us apart from some other funds that offer the same kind of support as well. I’d say, we are very entrepreneurial.

Just like every startup is different, investors also have very different teams in terms of their approach and working culture. One of the greatest compliments that I’ve heard from one of our startup CEOs was that he would define us as almost more entrepreneurs than investors.

What it means is that we don’t just sit on the board controlling the company’s cashflows. We join the CEO in figuring out how to make that company successful. We are actively helping, if the startup management wants this kind of a hands-on approach. Having been serial entrepreneurs ourselves, we are bringing this attitude into our investor roles as well.

Debiopharm Innovation Fund is continuously looking for ambitious entrepreneurs in digital 
health within evidence-based and regulatory environment (consumer products and wellness are 
outside of the Fund’s investment focus). Join Frontiers Health conference 
on November 11-12th in Milano or online and get a chance to network 
with Tanja and her colleagues!

Led by Henrik, health innovation hub is a Federal Ministry of Health think-tank which, among other projects, is coordinating the work on the famous Digital Healthcare Act (DVG) adapted in 2019 in Germany. One of the Act’s most discussed implications is the DiGA Fast-Track process that allows digital health applications to be approved for statutory reimbursement and available by prescription.

In this way, digital health startups that successfully go through the DiGA process get an opportunity to access the market of 75 million people who are enrolled across 105 public health insurance companies in Germany (read about DVG and DiGA in more detail here – editorial note).

Today we are looking at the first results and discussing further plans.

Henrik, before we dive into the facts, how are you feeling looking one year back?

First of all, we are extremely happy that we actually made DiGA happen, and I believe I can say that on behalf of the German Ministry of Health, BfArM (the Federal Institute for Drugs and Medical Devices that is in charge of approving DiGA – editorial note), us at health innovation hub and everyone else involved in the process.

When the first draft of this law became public a two and a half years ago, it received a lot of resistance from the very traditional part of the healthcare sector. We heard opinions that it was very unlikely for such a law to come through, that the physician was the only true institution to take care of health, and that digital health was not going to make a change.

Hence, I would say DiGA is a real breakthrough since we now have a clear path that any digital health application manufacturer needs to undergo in order to obtain the opportunity for reimbursement by a German health insurance.

In the meantime, we learned a lot, which is also great. We underlined from the very beginning that DiGA would be an agile process of mutual learning, and we have adjusted already to some extent in the past 12 months.

I’m particularly happy about the fundamental mindset shift of many healthcare providers that resulted from DiGA. We especially notice it in discussions with stakeholders of this very diverse healthcare sector: there is an understanding that digital health is happening and is here to stay. The question is no longer “do we need digital health?” but rather “how do we need to adjust our health system to the new digital reality?”

In my perspective, this shift in mindset is one of the biggest implications of the DiGA Fast-Track so far.

What is the current number of approved DiGAs and which therapeutic areas do they cover?

To date, we have 20 DiGAs in the registry. Especially interesting is that 75% of them are listed preliminary because they do not yet have all the evidence in place, but they have 12 months to present it to be listed permanently.

If we did not have the option for startups to generate the evidence while being listed, we would have a very limited number of DiGAs currently in the pipeline. Hence, it was a good move.

I’d like to note that the manufacturers which didn’t make it into the fast track were mostly rejected because their study design was not appropriate. Thus, the way they wanted to generate initial evidence was simply not sufficient. To me, it’s a very thorough argument that BfArM is making sure non-scientific evidence doesn’t infiltrate the health care sector.

Regarding therapeutic areas, we see quite a variety covering mental health, neurology, oncology, cardiovascular, and others. This diversity is exactly what we hoped for and expect to see even more variety in the future.

Around 30% of approved DiGAs are in the mental health area. What could be the reason for this significant share, in your opinion?

In Germany, patients typically have to wait an average of six months to see a therapist or psychiatrist. Hence, there is a big need for psychological help, so an app can be an effective support tool for bridging the gap between an initial GP diagnosis and the first expert visit.

Covid was also definitely a very important demand driver, but I believe the mental health industry already had a number of digital health applications in place, so they acted quicker than many other sectors.

What can you tell us about the actual prescription rate? According to a Research2Guidance white paper, DiGA manufacturers “see an immediate growth in downloads after DiGA listing, but the growth does not appear to be sustained in the mid-term”.

Unfortunately, there is no structured data generation around prescriptions. The figure we rely on is 20,000 DiGA prescriptions to date, which has a lot of potential, considering prescription rates are growing over time.

According to TLGG Consulting, for July 2021, the most prescribed apps were Vivira (orthopedics), Kalmeda (neurology), Zanadio (cardiovascular), and Somnio (sleep disorders) – editorial note.

What we’ve heard is that for the first half of the year, it was difficult for doctors to get any information directly from DiGA manufacturers. Doctors simply did not receive alerts from the startups. Consequently, it was challenging for doctors to try the apps because there were no healthcare professional test accounts.

Unlike pharmaceutical companies, which have a very established system for how to inform doctors, the DiGA startups simply didn’t have this practice of approaching HCPs directly. Many startups had never any direct contact with the healthcare system as such, so it took some time for them to build up those capabilities.

Nowadays, this has very much changed and there is not a single DiGA without a test account. DiGA manufacturers have learned that they need to educate doctors about this entirely new category of therapies.

And again, it has only been 12 months since the first applications were received, which means we do not even have a full year since the first DiGA was actually prescribed. Price negotiations with the startups will begin only after this first year. I would envision that prices will be lower – probably significantly lower – but volumes might then significantly increase. Thus, it is still a bit early to conduct a thorough analysis of prescription rates.

Let’s talk about international perspective around DiGA. Are there international DiGAs in the pipeline? Are there many countries interested in adopting similar processes?

Currently, all approved DiGAs come from German-speaking countries, but BfArM reports a growing demand from international DiGA manufacturers, including many outside of Europe. We have a lot of interest from the US, Canada, Japan, Australia, New Zealand, Singapore, China, and Korea. Hence, I would be surprised if 12 months from now, we don’t have a diverse mix of DiGAs in the registry.

Then, we are constantly getting requests from the countries that would like to learn from DiGA experience and replicate it – you do not need to reinvent the wheel each time you build a digital health process.

Together with several EU countries, we are now working on a broader alliance with harmonized digital health policies. It is a big step ahead for the startups targeting the EU market, which would mean that evidence needs to be generated only once, CE product certification needs to be received only once, and if approved by DiGA, approval in other countries is automatic.

hih is hosting the English-language “EU DiGA Con” on November 2^nd 2021 as part of their two-days “Digital Medicine Conference“. The DiGA Fast Track process will be explained in detail, and representatives from various EU countries will discuss their DiGA alike approaches and fathom harmonization possibilities.

It’s a very important and also challenging task. The good news is that the regulation of digital health is completely new for any healthcare system, which makes it more open to harmonization. Hopefully, we will be able to see the first results in the next 2-3 years. Obviously, the market potential of such an alliance would be significant.

Lastly, I would like your opinion on the role of DiGA, and DVG Law in general, in transforming the status quo of the healthcare system actors such as doctors, patients, pharma, and insurance companies.

If we look into the doctor-patient paradigm, so far, the majority of DiGA manufacturers have been focused on doctors because they are the decision makers who prescribe the app, and adherence is probably higher when the prescription comes directly from them. Conversely, I am curious if we will ever see DiGAs who approach patients and motivate them to contact either a doctor or health insurance company.

Ideally, we should allow patients to own the maximum information about their health, using electronic patient record (DVG Law also introduces the online consultations and electronic prescriptions into use – editorial note). In such case, we can expect that patients are also prepared to take their own actions around their health, which may include also directly approaching doctors saying, “I have this condition and would like to have this DiGA prescribed.”

We are still years away from having honest discussions about healthcare system roles. Most stakeholders somehow hope their daily business will remain the same, just with more digital solutions around it. This is highly unlikely. Roles will change significantly. The more information, power, and support we give patients in everyday life, the more transformation around the roles of healthcare professionals and health insurance we will observe.

Flash Poll: The Future of DiGAs

In order to provide you with more insights into the future of DiGAs, we asked Henrik to give a short comment on each of the theses, published earlier by TLGG Consulting:

The hero of our story is Giuseppe Riccardi, a Full Professor in Computer Science and Information Engineering in the Department of Computer Science and Information Engineering at the University of Trento, Italy. Giuseppe is a pioneer in natural language understanding and conversational human-machine interaction who has applied his research in the health domain.

Giuseppe, please tell us more about your background and research focus.

I joined the University of Trento in 2005 after coming back from the United States, where I had spent 15 years working at Bell Labs – the place where most innovation was happening before the start of the 21^st century. At Bell Labs, I dedicated my attention to various research problems in speech and language processing in different roles, leading the deployment of the first naturally speaking conversational system in the world, codenamed “How May I Help You?”.

Upon returning to Italy, I extended my research agenda in artificial intelligence to include the investigation of all signals exchanged by humans in their interactions, including natural language (speech, text, and multimodal) and physiological signals. The main goal of my research is to design and train computers in all forms (like smartphones, smartwatches, and robots) to live and work with humans and make their world better.

In the last 15 years, I have extended my efforts to AI applications in the health domain. I am running an interdisciplinary research lab called Signals and Interactive Systems Lab that unites approximately fifteen people, including students, postdocs, and research engineers with electrical engineering, computer science, computational linguistics, and psychology backgrounds. We are studying the signals generated in human interactions and collaboratively do concept and test prototyping with healthcare professionals, hospitals, and companies. Our lab has been part of various international research projects, including CO-ADAPT. (CO-ADAPT is a European research project centered around active aging with the use of conversational agents. You can read more about it in our interview with Dr. Giulio Jacucci – editorial note).

How long will it take for AI to reach mass adoption in healthcare? Nowadays we talk more and more about the accelerated application of technologies in health. Is the future of this mass adoption already here?

In my opinion, we still need quite some time. Let’s go back to pre-pandemic times, 2009 to be exact, and have a look at one example. I was already a professor here in Italy and I was invited to collaborate on a well-known IBM project called IBM Watson. As you may know, a few years after IBM Watson beat the champions of “Jeopardy,” having an impact in healthcare became the major objective for Watson. (IBM Watson thoroughly defeated two human champions in the game of Jeopardy in 2011 – editorial note).

Just think about it: a huge company like IBM, with all its resources and impressive research facilities like Yorktown Heights Research Center, sets up an agenda to have impact in health. By now we all know it did not go as expected in the sense of having a huge impact (you can read more about IBM Watson Healthcare case here – editorial note). Rather, it was a story of figuring out why it’s so hard to do – and it took around ten years to understand what the issue was. In research, we know that failure is part of the path to success.

And what is the issue, in your opinion? What are the key factors in AI adoption and more generally, in healthcare transformation?

I could say that in the last fifteen years I’ve learned transforming healthcare is really about setting an equation where you need to include “the people” as well as the latest and greatest from AI and other fields. An example that comes to my mind here is a pilot on hypertension that we did in an Italian hospital in Turin to monitor the psychological state of patients using AI and various sensors and wearables. The objective of the pilot was to establish and analyze a correlation between the patient’s psychological state and hypertensive state (you can check this link for more publications on the subject – editorial note).
What we realized during this pilot was that the patients were eager to share their problems and their data to understand the cause of hypertension. On the other hand, we found it more difficult to interact with the healthcare system and to interject at particular points of a patient’s journey. Of course, there is a big data problem as well, but from my perspective, the biggest and most understated problem is the human factor. You have all kinds of people in the hospital, from nurses to internal medicine MDs and surgeons, very different kinds of people, and many are concerned about the use of AI or other technology because they fear their work and role could change. This is a natural human response to novel events that may be threatening.

That’s why in our projects, we are looking for champions or early adopters: people in the healthcare system that are open to designing new pathways in the future and to implementing changes in the way they work and make their decisions. Hence, another crucial aspect is establishing new processes in the patient’s pathway: integrating into the hospital’s pipeline and changing the protocols to transform the way it works. An important advantage of the technology that comes with AI is the ability to measure the value of human decisions and behaviour, so AI systems can provide feedback and we humans can learn over time to change both, if necessary.

The current state of affairs in hospitals is that you have little empires, in a way, that don’t work organically amongst themselves or with inpatients and outpatients, yet the hospital is a really big place to do innovation. That’s why I would also underline the importance of creating synergies between people inside and outside the healthcare organizations and between people and technologies. For example, the above mentioned CO-ADAPT project where we use Personal Health Agents (PHAs) to engage patients in conversations and support psychologists in improving users’ mental health. It’s a very good case of establishing synergies and cooperation between people – HCPs, psychologists, patients, and AI scientists – and technology. PHAs transparently connect users and psychotherapists to provide so-called blended interventions. This is a first-of-its-kind intervention in the world using AI to help people.

How do we deal with the trust issues around AI? It becomes especially important when we talk about conversational agents who collect information about the day-to-day routine of patients.  

It is a complex issue and, in my opinion, trust has multiple facets. First of all, I see trust in connection with the utility function, maximized by a certain service or product. Think about Gmail: we all use it without actually reading any contract, even though our emails are analyzed by AI that provides suggestions on the composition of the phrases in your text. But we trust it in a way. That “way” is your personal utility point value. If that does not satisfy you, you stop using it, although it is difficult nowadays. Then there are macro processes at the societal level that determine the minimum trust level that society would set and discipline through government regulations.

In our research and experimentation, in addition to national regulations and ethical committee guidelines, we make sure that users are fully aware of the AI systems they are interacting with and who is responsible for their actions.

What are key aspects where AI is especially helpful when applied in healthcare?

First one is persistence. AI offers you a tool in the form of pervasive intervention: for instance, you can consult with your PHA on your everyday nutrition and exercise choices. PHA can stimulate a positive change, especially important for chronic disease patients, like hypertensives and diabetics. Obviously, there is no doctor who could follow and monitor you 24 hours a day – but PHA can.
Another recent project I’m involved with is in collaboration with Anffas Associazione Nazionale and funded by the TIM Foundation focusing on helping autistic people with Asperger’s syndrome to manage their everyday routines and problematic situations. People with this condition may have difficulty interacting socially, and something like not understanding a joke can be dramatic for their self-confidence. We are designing PHA that would support these users, help them not feel alone, and support them during the day. We are developing a truly organic artificial intelligence that interacts with users and their caregivers that can teach PHA over time to improve its problem-solving support.
The second aspect is scalability. The pandemic has made the challenge of scalability especially visible: how can we help a large set of the population with limited resources? Clearly, PHAs are a huge asset for scalability of healthcare services such as blended mental health interventions, which have been tested during the pandemic in the CO-ADAPT project along with IDEGO Digital, a company spearheading digital psychology.

Judging from your broad international experience in research and application of AI in healthcare, can you outline the main country-level differences in the field?

On the side of the research, I don’t see major differences. However, I do see them at the funding level: there is definitely much more research and venture funding available in the US than in Europe, especially at the national level in Italy. To give you some context, at the University of Trento, our Department of Computer Science and Information Engineering is very strong in AI, a top one in Italy and in the top 100 worldwide. Getting the kind of venture capital funding that would be accessible for us in the US, we could launch at least two startups per year in AI and related subfields.

Then, there are some cultural differences. In the area of mental health, for example, the US and Nordics markets would be more suitable for testing technologies and products because there is much less stigma around mental health issues than there is in Mediterranean countries. However, I think, the pandemic may have started some cultural changes in this respect.

If we talk about the regulatory aspect, the US approach is very different from the European one. In the US, the regulations are based on evidence: if the product is effectively working and is being used by the patients, the regulations are created in the favourable direction. In Europe, the regulations are done from much more administrative perspective with the aim to audit the products. In addition, the  EU draft AI regulations released at the end of April may create a burden on big companies that were looking into the cooperation or acquisition of startups because they may assess a higher risk in jumping into the partnerships with AI startups – and this may slow down innovation.