Healing the health divide for women

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Lee Landenberger: The Bioworld Insider Podcast.

Lynn Yoffee: This is The Bioworld Insider Podcast. I’m Lynn Yoffee, Bioworld’s publisher. The health of half the people in the world is underserved. Beyond a narrow focus on reproductive health, progress to advance women’s health in general has been surprisingly slow. What’s been poorly understood is that many conditions disproportionately impact women. Other conditions and diseases affect women in different ways than men.

In Bioworld’s new investigative report, we found that decades of research excluding women from clinical trials and investment decisions in male-dominated boardrooms have ignored these facts. Of the drug development companies working on women’s health solutions, the proportion of funding and partnering for the sector is quite small. Without investments, nothing moves forward.

Today on the show, we have Karen Carey. She’s Bioworld’s managing editor and chief analyst. She examined investments and company pipelines around women’s health. The results are discouraging. Also joining is the managing editor of Bioworld Science, Dr. Anette Breindl. She brings perspective on why and how research has been stunted. Welcome Karen and Anette.

Anette Breindl: Pleased to be here.

Karen Carey: Thank you. Glad to be here.

Lynn: They’re here today to chat with Lee Landenberger, a Bioworld staff writer and The Bioworld Insider Podcast host. Lee, over to you.

Lee: Lynn, thank you very much. I really appreciate, Karen and Anette, I appreciate you being here. Anette, I wanted to ask you a question first. I read this series. One of the sentences that jumps out at me early on is the historically consistent use of males as a biological standard in research has hindered insights into conditions that affect females, which is a long– it’s an accurate way of putting it, but it’s a long way of saying there’s bias out there that is stopping development. Can you talk to me about the bias that you encountered when you were doing your research and why we have come to this standard?

Anette: Historically, of course, more scientists have been males. Science is a deeply human endeavor, right? It is meant to be dispassionate. The observer is meant to be separate from what is being observed. Scientists are people like everybody else. Like everybody else, they bring their own story into their work. It did not historically maybe occur to men even that women are very different.

Then there’s also the idea, historically. There is some truth to that because females, and that is not just women, but female animals have an estrus or menstrual cycle that the hormones are very different at different times of the cycle, and that this would make it more complicated to observe that this would muddy the waters of what you are trying to observe.

In research, you are always trying to standardize your conditions. The problem here is that you are standardizing them so much that you are standardizing out something that is extremely important because these things do affect health.

Lee: Women’s health, this is also mentioned in the series. Women’s health has often been thought of by many people, developers, investors as coming out of the bikini area. People laugh and roll their eyes when they hear that phrase, but it is sort of true. It’s been a guideline in the past. It still evidently seems to be somewhat of a guideline in what’s going on now. Would you agree with that?

Anette: Yes. I do think that a lot of women’s health still focuses on, as you said, it’s called the bikini area, which is funny and descriptive, but at the same time, just far too narrow a way of looking at women’s health. People think of women’s health as the things that only happen to women, right? Something like ovarian cancer. Basically the things that only happen to women, of course, things that affect the reproductive tract. Then to a lesser degree, breasts. Breast cancer is also almost specific to women, right? There are actually cases of male breast cancer, but very, very few.

Lee: Would you talk to me a little bit about the main diseases that affect women disproportionately or ones that look different in women than they do in men?

Anette: Those are the other two areas, really, of women’s health, which can be split into these three areas. The truly women-specific diseases that everybody thinks about, and then the ones that are more likely to affect women than men, and the ones that affect both women and men, but they just affect women differently than men. An example of diseases that disproportionately affect women, a big one is Alzheimer’s disease. Women are more likely to get Alzheimer’s disease than men. That is not just because women live longer. They are just also at greater risk at a given age of having Alzheimer’s disease.
At the same time, they are not included in clinical trials at the rates that would reflect their increased risk. It becomes something of a vicious cycle. It’s hard to figure out why women are at greater risk if you’re not including enough of them in clinical trials, and so they continue to be at greater risk. Then, yes, the third thing is diseases that affect women differently than men.

Here, cardiovascular disease is a very typical example. With men, there is narrowing of the arteries that is very obvious, and you can see it in imaging. You can see, “Oh, there’s the place where the blood flow is restricted. With women, you don’t really see that. There is not this one place where it is restricted in an artery. As blood flows along the artery, as you get to the microcapillaries at the end, there is also reduced blood flow. What seems to be happening is that the restriction is more along the entire artery as opposed to one place where there is an obvious restriction happening.

Of course, if you’re looking for these obvious areas where the capillary is narrowed, in women, you’re not going to see them, and you’re going to think, “Oh, she doesn’t look like she has heart disease,” but she does. It just looks different. Again, if you’re trying to develop treatments, and you develop them for the way the disease looks in men, those are not necessarily going to be as effective for women.

Lee: When you were researching this and writing it, were there surprises, things that jumped out at you? For instance, the complexity of the biology, was that something you expected going in?

Anette: One surprise to me was that we really still don’t know that much about these differences. Despite the fact that the NIH has mandated the inclusion of women in clinical trials for a while, and is now also mandating the inclusion of females in animal studies, it has just been slow going. There is a lot still that is not known. One thing that I thought was sobering was that I interviewed a researcher not too long ago who had published a paper on sex differences. He said that he was really surprised to find them.

He was talking about the idea that, “Oh, it’s really important to include female animals in research, because otherwise we would have never found this,” but it seemed to be a new idea to him despite the fact that, like I said, the NIH has been mandating this for a while. I felt like we are perhaps not as far as one would like in even having a general realization of the importance.

The other thing, on a purely scientific basis, what I found very interesting was that the X chromosome affects these sex disparities a lot. It is something that is– in my story, I said, it is hiding in plain sight, because on the one hand, of course, we know that, really, the standard way to tell apart males and females, to a first approximation, it is a pretty good assumption that if somebody is female, they are going to have two X chromosomes, and if someone is male, they’re going to have one X chromosome and one Y chromosome. There are exceptions, both chromosomally.

Then there are, of course, transgender individuals whose gender identity, for whatever reason, does not conform to their chromosomal sex. Still, it is, for most people, that’ll work. If they have two X chromosomes, they’re female. If they have an X and a Y, they’re male.

Now, one of the female X chromosomes is silenced during development so that females don’t have twice the proteins of the X chromosome which would give you a dosage problem with many things. I had not realized that silencing is really very imperfect so that women can have higher levels of proteins that are expressed on the X chromosome because the silencing is not perfect.

The other thing that I had not known that really surprised me was that long non-coding RNA that silences one X chromosome in female cells, that binds to a lot of proteins, and that these protein RNA complexes include many auto-antigens apparently, which is thought to be one reason why women are at higher risk for a lot of autoimmune diseases.

Lee: Karen, you ran the numbers. You probably came across some surprises too. I know one of them for me was I thought venture cap funding might be surging in this. I was surprised to see that it wasn’t. Can you talk to me a little bit about venture cap funding in women’s health?

Karen: Absolutely. I was actually surprised that it was where it was when we started looking at it. It does look, to me, there have been some strides made, but we’re slipping back a little. Through September, it was $1.78 billion raised through VC financings of companies working on women’s health biopharma products. Now, that compares to $3 billion for all of last year and more than $10 billion in 2021.
Now, how we came up with this is we identified biopharma companies that have worked on women’s health biopharma products, and we cross-referenced them with our database of VC financings. These companies that we identified, they might be working in various other areas that have nothing to do with women’s health. The money raised through financings may be going to other programs outside of women’s health. If they raised money, we counted it, recognizing that a business that does well in one area can advance programs in other areas. There’s sort of a ripple effect for women’s health efforts from those companies.

The VC financings were from 1999 through September of 2024. We found a total of 917 VC financings that fit our criteria. All told, they raised a combined $44 billion. Now, when we laid that out by year, we noticed two things. VC funding of women’s health companies began to rise around 2015. Now, that is around the time that the NIH began to ramp up its efforts to make sure women made up half of clinical research participants among NIH trials. It’s also around the time that Congress put into law the 21st Century Cures Act, which directed the NIH to develop clinical trial standards to advance women’s health.
Moves were being made by government. The private sector was paying attention. VC financings for women’s health companies went from $891 million in 2014 to $3.2 billion in 2015. With the exception of 2016, they kept rising through 2021. Then they dropped off in 2022. Went back down to $2.4 billion. The other thing that we noticed when we laid it out by year is the proportion of money going into women’s health companies.

If I look at 2015, companies working in women’s health made up about 31% of all VC financings that year. That, again, dropped off all the way to 10.8% in 2022. Then it rose up to 15% in 2023. Then back down to 9.6% this year. That’s in line with the 10% of the NIH budget in 2023 that was spent on women’s health.

Lee: When companies are out there trying to get noticed for developing women’s health therapies, what do they need to do?

Karen: Trish Costello, she’s the founder and CEO of Portfolia, a VC firm focused on women’s health. She told me they look for experienced teams that can navigate regulatory challenges, bring products to market, add value quickly. They’re looking at investments with a strong market potential and valuation growth that allows them to exit within about eight years. Now, that is not long enough for biopharma. What that means is a lot of med tech companies get more investment than biopharma companies. It’s much harder for companies working on therapeutics to raise money because it takes so long to develop a drug.

Another person I talked to, Anna Zornosa-Heymann, she’s a women’s health investor who also is a contractor with the NIH’s SEED office. She said that it’s a challenge to convince investors to invest in biopharma products in women’s health for the same reasons. Digital med tech assets can reach the market in a few years, and show an immediate revenue stream. For companies working on therapeutics, they have longer development and regulatory cycles.

I also heard that women’s health is often considered a riskier or less profitable market, partly because the data does not exist. There are no comparable precedents for market success. Women are half the population, but only about four percent of all health care R&D goes toward female-specific needs. That scares investors. They see things as too complex and they back away.

Lee: Where do women’s health investments going in the future?

Karen: The investors I talked to still seem somewhat upbeat about the future. You can see by our data that some of these companies are getting funded. That four percent of health care R&D that I mentioned, that’s risen by 10 times of what it was in 2017. Things are moving in the right direction. These VC funds that are exclusively focused on women’s health. While there are only maybe about 12 or so of them now, there were none a decade ago. A few of them are specifically focused on female entrepreneurs as many women’s health companies are led by women.

I heard there is a bit of a chicken and an egg situation, which comes first. You’ve got young companies with good scientific ideas. They’re struggling for funding. Then you’ve got those with money wanting to see things a little further along in the clinics, some human trial evidence. If some of these companies with good ideas and strong science start to have impressive exits, either acquisitions, or IPOs, there can sort of be a snowball effect for others working in the space.

We may start to see more investors. The bottom line is it all starts with the dialogue that we’re having right now. People are talking about it more. Government is making efforts. New women’s health focused investment firms are cropping up. There is an ecosystem that is building here.

Lee: Is the number of women’s health companies growing?
Karen: Yes, that too. The Office of Research on Women’s Health at the NIH, they have found that half of the 1400 women’s health companies that exist today in the US were established in the last five years. Our analysis found that there are 1028 companies working on 2161 women’s health products. The most active companies are actually the largest pharmaceutical companies. Just the fact that there are more VC investors active in this space means that there are more companies vying for the funds.

Lee: Okay. Got it. Lynn, did you have any questions you’d like to ask them?

Lynn: No additional questions, but I will tell our listeners that you can read the entire series on bioworld.com. Just go to the Special Reports tab and look for the Women’s Health Special Report. We hope that this special report will help to highlight the value propositions around the strategies to improve the health of women around the world. We hope that scientists and industry leaders alike will more broadly take on these critical challenges that impact humanity as a whole.

That’s our show for today. As always, BioWorld will continue to keep you informed of all the most important scientific, clinical, regulatory, and business updates. We’re a daily news service covering the development of the most innovative human therapeutics designed to improve the human condition. If you need to track the development of drugs, turn to bioworld.com. You can follow us on LinkedIn or X. If you want to share news with us, drop us an email at newsdesk@bioworld.com. If you’re enjoying this podcast, don’t forget to subscribe via your favourite platform. Thanks for joining us today.

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