Could this be the end of condoms and will men embrace the hormone-free birth control pill?

Bakshi shares the innovative approach of YCT-529, the results of their Phase 1a study, and the anticipated impact on reducing unintended pregnancies. This conversation highlights the significance of male contraception in the broader landscape of reproductive health and the challenges faced in pioneering such a transformative solution.

What inspired you to develop a hormone-free birth control pill for men?​

My co-founder, Nadja Mannowetz, and I originally focused the company on the development of a hormone-free female ​contraceptive. It was when we were working in this space that we learned first-hand how negatively hormonal contraceptives impact women.

We had the opportunity to pivot our female contraceptive into a Covid antiviral in early March 2020, when it was assumed that there would be very few cases with little to no impact on global health. In less than a month, the Covid candidate outraised the female contraceptive company, even though the female contraceptive had a cleaner shot to getting to a blockbuster at the time. Given the funding that the Covid antiviral company received early on, this company was ultimately acquired in less than 9 months.

When we thought about how to decrease the hormonal burden on women, and still find opportunities investors would be interested in, we realized male methods of contraception could be an opportunity. And we are fortunate that this thought turned out to be true.

Can you elaborate on how YCT-529 works to prevent sperm production?​

YCT-529 inhibits retinoic acid receptor-alpha. This target is required for the development of sperm cells, but also for the release of mature sperm cells. By inhibiting these two important steps we have a belt-and-suspenders way to decrease sperm counts and thereby prevent pregnancy.

What were the key findings from the phase 1a study of YCT-529?​

The key findings of the Phase 1A study were that doses as high as 180 mg were safe and well tolerated in men who received drug.

Also, the pharmacodynamics of the drug allow us to believe that the pill for men may be more forgiving than the female contraceptive pill. The female pill requires users to take the pill every 24 hours, but this is not always achievable. Yet the male contraceptive looks like it could be taken with some wiggle room (maybe at some point within the day rather than 24 hours after you last took the dose).

How does YCT-529 compare to previous attempts at male contraception, particularly the hormonal male pill developed by WHO?​

YCT-529 is similar to previous attempts at male contraception in that we are using an agent that inhibits spermatogenesis (the development of sperm). One key difference is that we are using a non-hormonal active agent that does not change the hormonal profile of the user. As a result, we do not anticipate side-effects as shown in the previous WHO study.

What are the next steps in the development and testing of YCT-529?​

In the next clinical trial, we will assess the safety of this drug when given for a longer period. We will also assess changes in sperm parameters, which will give us a glimpse into the efficacy of our molecule!

How do you foresee YCT-529 impacting unintended pregnancy rates in the US?​

Unplanned pregnancy rates in the US are nearly 50%. On top of that, consider that 34% of unplanned pregnancies end in abortion​. When women who sought an abortion are asked if they used a contraceptive, nearly 50% say that in fact they were contracepting. When asked what contraceptive they were using, 60% of these women say they were depending on their male partner’s condom, which failed: meaning roughly 25% of all women who seek an abortion do so because the condom failed them! The condom is the only reversible contraceptive men have access to. The lack of innovation in male methods has negatively impacted women. The development of an improved male contraceptive that doesn’t have to be used in the moment, would improve outcomes for women, and hopefully bring down both unplanned pregnancy and abortion rates.

What challenges have you faced in the development of YCT-529, and how have you overcome them?​

YCT-529 is first of its kind. Nobody has developed a hormone-free contraceptive pill for men. And so, firsthand we are experiencing the first questions from regulators and various acquirers. Questions like: why should men take on any risk when using a male contraceptive since they never get pregnant? This results in interesting conversations about how high the bar for efficacy needs to be, and how much this drug should be without side effects. We also hear suggestions that men won’t be willing to take on any side-effect profile and therefore, won’t be willing to take on the responsibility of family planning (and these are comments coming from leaders of pharma companies with women’s health teams). And yet men who use Viagra have blurry vision and potential cardiac risk to prevent erectile dysfunction. We see that gay men use Truvada, which has potential liver toxicity or bone density loss to prevent getting HIV.   

Can you discuss the significance of the $12M Series A funding from the Male Contraceptive Initiative?​

Our Series A is perhaps the third largest round of funding ever obtained for a private company in the contraceptive field. And then there’s us. It’s a big deal to have the backing of MCI, but our $15M series A was backed by Future Ventures. And we expect this cash to allow us to read out at least one other clinical trial, which would be the one where we look at the safety of repeat dose administration and expect/hope to also get a glimpse into efficacy (reduction in sperm count).

How do you address concerns about potential side effects or long-term impacts of YCT-529?​

Of course this will be something that we monitor, but to date, we have dosed monkeys, our most similar species, for 108 days with zero safety concerns.

What feedback have you received from potential users and the medical community about YCT-529?​

We get tons of emails from men and women who express an interest in either directly participating in the clinical trial or women asking if they can pick up samples for their husband or enroll them in a clinical trial. It’s wild! But it also gives us the confidence that we are on the right track, and that we have the opportunity to support couples in their family planning journey!

I think the demand is so high, I’m looking forward to when this product is eventually on the market!

How does YCT-529 align with the current landscape of women's reproductive rights and the need for more male contraceptive options?​

No doubt, women’s reproductive rights are narrowing. This month marks two years since the dissolution of Roe vs. Wade. Women’s contraception is now under fire in several states. As we saw in the Dobbs case, Justice Clarence Thomas suggested that we consider whether we should continue to allow coverage for female contraceptives under the ACA (or Obamacare).  This can only happen because there are currently no male contraceptives available. If there were, it would be a lot harder for a Justice to easily suggest we decrease access to one contraceptive without decreasing access for another population. In this sense, YCT-529 will give couples a choice to share the burden of family planning and could also protect women’s access to various contraceptive options.

What is your long-term vision for YourChoice Therapeutics and the future of male contraception?​

The long-term vision of YourChoice is to get YCT-529 approved as the first hormone free birth control pill, make sure this product is covered by ACA and resume the development of hormone free contraceptives for women.