Rethinking infertility treatment: Treating couples, not just women

Governments around the world are becoming increasingly concerned about the decline in birth rates and their consequent effects on population. Across the member nations of the Organisation for Economic Co-operation and Development (OECD), the average birth rate in 2022 was 1.5 children per woman, well below the value of 2.1 required to maintain a steady population. Regardless of whether population decline constitutes an economic crisis for societies and an existential one for humanity, no single company or industry can solve these problems. 

However, infertility is indisputably a major factor contributing to declining birth rates, with about 1 in 6 couples worldwide struggling to become pregnant due to infertility issues. These couples are not sufficiently served by the current treatment paradigm, which centers on in vitro fertilization (IVF) and has not substantially changed in over four decades. Improving the standard of care in infertility treatment for infertile couples is something the biopharma industry as a whole, and Igyxos Biotherapeutics in particular, can do.

IVF: A gold standard of infertility treatment that needs improvements

Since its introduction over 40 years ago, IVF has been regarded as the gold standard among assisted reproductive technologies (ARTs) for treating infertility. IVF involves stimulating a woman’s ovaries with hormone treatments to produce healthy eggs (oocytes); retrieving the eggs via a surgical procedure; fertilizing them ex vivo with sperm; then transferring the fertilized eggs back to the woman’s uterus. Follicle-stimulating hormone (FSH), a hormone involved in the production of both oocytes and spermatozoa, and its analogues are most frequently used for ovarian stimulation.

Although IVF has helped countless couples become pregnant, it has major drawbacks. It is expensive: a single cycle in the U.S. costs $20,000-$25,000. More importantly, it places the full physical burden of treatment on the woman by requiring her to endure painful daily hormone injections, which can have significant side effects. These protocols alone lead to discontinuation rates as high as 35%.

For women who do complete one cycle, only 25-30% become pregnant. Contrary to popular perception, multiple IVF cycles are no guarantee of success: four cycles have a success rate of only about 60%. Further, success rates have declined over time because more women are postponing maternity until later in life and increased age in the woman reduces the odds.

Various advances to IVF treatments have been introduced over the years, including recombinant FSH production and a long-acting version of FSH that reduces the number of injections needed. However, these advances represent only modest, incremental improvements to the core IVF process, not innovation around new mechanisms of action. 

This lack of innovation does not apply solely to female infertility. Overall, the issue for couples is not only the woman’s fertility but also the man’s that contributes to about 50% of all cases  – and there are no approved therapies to treat male infertility. Men have long been the “forgotten half of fertility” and innovation is needed to address this issue.

Remembering the forgotten half: An epidemic of male infertility?

Twenty years ago or so, male infertility was not widely acknowledged or discussed. This reticence was driven by several factors: a lack of data highlighting prevalence of the problem; social stigma, stemming from associations of virility with fathering children, that led men to feel shame and avoid medical care; and a gender bias that framed infertility solely as a “women’s issue.” 

This is not to suggest male infertility was entirely ignored. Intracytoplasmic sperm injection (ICSI) was introduced in the 1990s to help men with low sperm counts or motility. ICSI is an ex vivo procedure in which a selected sperm cell is injected directly into the egg, thereby increasing the odds of fertilization. However, an often forgotten aspect of ICSI is that it still requires the woman to undergo IVF, even though she is not infertile. Additionally, ICSI does not address the underlying cause of male infertility.

As noted above, FSH plays a key role in gametogenesis in both women (folliculogenesis) and men (spermatogenesis). FSH injections either three times per week or every other day have been explored for treating male infertility. Because the spermatogenesis cycle lasts about three months, men require 30 to 45 FSH injections – many more than women. Although not approved for male infertility, FSH treatment has yielded some results but it is still inconvenient and stressful.

More recently, there have been efforts to repurpose approved drugs to treat male infertility and promote spermatogenesis, but so far they have not met with success.

Today, a large and growing body of data demonstrates an ongoing decline in male fertility across many countries, with multiple lifestyle, environmental and health factors considered potentially causal. These data on male infertility, accompanied by increasing awareness that it affects about half of infertile couples, has catapulted the topic to the fore for physicians and their male patients. There is now a major opportunity for treating this “forgotten half” of the fertility equation.

The need for a true challenger in fertility treatment

In its current paradigm, IVF is not able to meet the needs of both women and men for more effective, convenient and tolerable infertility treatments. Igyxos, a clinical-stage biotech, is a true challenger in a space that has not seen real innovation in decades. The company is developing a novel therapy, IGX12, that could directly address the growing problem of male infertility and also improve the odds of IVF success for women.

IGX12 is a unique treatment for infertility in both its modality and mechanism of action. It is a first-in-class humanized monoclonal antibody (mAb) that potentiates the bioactivity of FSH to promote more efficient binding of FSH to its cognate receptor, FSHR. By enhancing this binding interaction, IGX12 initiates a stronger signaling cascade that promotes gametogenesis. 

As a once-monthly injection, IGX12 could offer distinct advantages for individuals experiencing infertility.

• For women, IGX12 could improve the odds of IVF success without adding unduly to her treatment burden. By improving FSH activity beyond what high doses of FSH can achieve, IGX12 could  be used in women who are low responders to current treatment.
• For men, IGX12 could enhance sperm concentration with a few injections over the course of the spermatogenesis cycle.

IGX12 could treat men whose sperm counts fall below the thresholds required for a good chance of getting a woman pregnant. In these men, IGX12 could improve their fertility to a level that allows the couple to conceive a child naturally, without resorting to ART. But it could also be used in conjunction with ICSI, where it would help generate a higher concentration and number of spermatozoa as candidates for the ICSI procedure.

Thus, IGX12 is not intended to replace IVF and ICSI. As a novel addition to the traditional treatment paradigm, IGX12 could improve on the standard of care and boost the fertility industry as a whole.

IGX12 has completed preclinical studies, where it showed excellent results in vitro and in several animal models. IGX12 has also completed a Phase 1 single ascending dose (SAD) study in male and female volunteers that demonstrated an excellent safety profile. To complete its Phase 1, IGX12 is completing a multiple ascending dose (MAD) study in male volunteers with results expected by early December.

Treating couples, not just women

Infertility is not just a men’s issue. It’s not just a women’s issue either, although today it’s primarily seen that way. Infertility is a couples’ issue, and it’s high time it was treated as such. That is exactly what Igyxos is doing: developing the novel, innovative infertility treatment for infertility that couples deserve. By itself, IGX12 will not solve the larger societal issues of declining birth rates and populations. But it can be an important piece of that solution for couples who want to have children but struggle to do so. Igyxos is rewriting the rules of infertility treatment to give these couples a brighter and more hopeful future. We invite investors and strategic partners to join us in solving the infertility problem and creating that new future for millions of couples worldwide. To learn more about Igyxos and find our contact information, please visit https://www.igyxos.com/.