No. Soluble adenylyl cyclase (sAC) is a non-hormonal target, and its function is unrelated to hormone levels or activities. Plus, there is no indication from animal studies nor from studies of the humans who are missing sAC that inhibiting sAC will alter hormone levels. Therefore, there is little to no chance of side effects typically seen with hormonal birth control methods.

Sacyl is developing an on-demand birth control pill which men would take only when, and as often as needed.

Our proof-of-concept experiments in animals used a prototype sAC inhibitor. For the mouse studies, this inhibitor works approximately 15 minutes after treatment, and it provides 2.5 hours of complete infertility with >90% contraceptive efficacy for 3.5 hours. By the next day, the mice returned to normal fertility.

The Sacyl scientific team is currently identifying the best sAC inhibitor compound to advance into human clinical trials. Our goal would be a pill that starts working within 30 minutes and provides 100% contraceptive efficacy lasting 12-18 hours. Exact times will be determined during clinical trials.

The sAC inhibitor contraceptive effect lasts only as long as there is sufficient drug in the man’s body (and in his sperm). Like all drugs, the body metabolizes the inhibitor compound over time, and on-demand contraception means drug will only be present at effective levels around times of sexual activity. This type of dosing minimizes any potential long-term safety concerns, which is a clear benefit compared to treatments where people are chronically taking a drug. For the prototype compound we used in our animal proof-of-concept experiments, the amount of compound fell below its effective threshold level within hours, and it was effectively gone from the mice after 24 hours. The Sacyl scientific team is working on developing sAC inhibitors which will persist at effective levels for 12-18 hours.

In our animal experiments, we did not observe any long-term effect on fertility, even after repeated dosing. Thus, we do not expect to see any side effects emerge after men repeatedly use on-demand contraception. This expectation is also supported by the two men identified who have naturally occurring mutations which render sAC completely inactive throughout their bodies.

sAC inhibitors prevent sperm from swimming, and they also prevent a final maturation step that sperm must complete as they pass through the female reproductive tract on their way to meet the egg. So in the presence of a sAC inhibitor, sperm cannot reach nor fertilize the egg. The Sacyl family of sAC inhibitors are exquisitely specific for sAC; they do not affect any closely related human targets nor do they affect an extensive panel of other targets prone to elicit side effects from other drugs.
We now know that people and mice can live their entire lives without sAC anywhere in their bodies. In both mice and humans, the absence of sAC makes male mice and men infertile, confirming that sAC is essential for sperm to fertilize the egg. Besides being infertile, the only other problem experienced by the men without sAC was an increased tendency to form kidney stones, but kidney stones can only form if sAC is missing for years. With our innovative and unique on-demand approach, where a man would take a sAC inhibitor contraceptive only when and as often as needed, there should be NO SIDE EFFECTS. This will have to be confirmed with rigorous safety studies as well as clinical trials.

Sacyl’s on-demand contraceptive is the first of its kind. Other male contraceptives in development prevent functional sperm from being made in the testis. Because the process of making a functional human sperm requires between 2 to 3 months, men must continually take these types of contraceptives for 2-3 months before their sperm count would fall low enough where they would become infertile. And because sperm development occurs continuously, men taking this type of contraceptive would have to take the drug chronically. This applies to the hormonal methods currently in clinical trials as well as all the non-hormonal methods under development which target sperm production (spermatogenesis). With these methods, healthy men will have to take a drug continuously for what could be as long as decades to retain contraceptive effectiveness. In addition, once a man ceases taking any of these birth control methods, reversal to full fertility also requires several months.

That is among the unique advantages of the innovative on-demand approach which distinguishes it from all other male contraceptives in development. With on-demand contraception, the man takes his contraceptive pill 30 minutes before having sex, which means that he can take it in the presence of his partner. In contrast to other types of male contraception under development, which require the women trust that the man has taken his pill or applied his transdermal gel every day for the past month(s), with a sAC inhibitor male contraceptive, she sees the man taking his on-demand birth control pill.

We are currently working to improve our preclinical drug candidates, and we hope to start clinical trials in humans in 2025. Usually, the first phase of a clinical trial focuses exclusively on safety, but we have a unique advantage that we can also test whether the sAC inhibitor blocks motility of the subject’s sperm. If our clinical trials go well, this contraceptive could be in the market as early as 2031.

The target of this new treatment, an enzyme named soluble adenylyl cyclase (sAC), was discovered in 1999 by two of Sacyl’s co-founders, Jochen Buck and Lonny Levin. Fairly soon after its discovery (by 2005), it was known that sAC is an essential “on” switch for sperm to reach and fertilize the egg. Prior to ejaculation, sperm are stored in a dormant state, and upon ejaculation, they become activated, start swimming, and complete their maturation process so that they can reach and fertilize the egg. The target of this treatment, sAC, is absolutely required for each of these processes.

Despite knowing sAC is essential for male fertility since 2005, we did not start working on developing sAC inhibitors into a potential male contraceptive until ~2019. Contraceptives are taken by healthy individuals, which means that side-effects cannot be tolerated. At the same time we showed that sAC is the essential “on” switch in sperm, we also found that the sAC is expressed in other tissues of the body. The fact that sAC was found in other tissues besides sperm raised concerns that sAC inhibitors might have effects on other tissues outside of sperm, and this prevented us from pursuing sAC inhibitors for contraception. Two remarkable discoveries in 2019 reignited work towards a male contraceptive based on inhibiting sAC. First, two men were identified who have naturally occurring mutations which render sAC completely inactive throughout the body. These men are sterile, but otherwise healthy. These two men taught us that a person could have absolutely no sAC anywhere in their bodies and while men would be infertile, they would have nothing else significantly wrong with them. Second in 2019, we had our first indications that a single dose of a potent and selective, fast-acting inhibitor of sAC into a male mouse could render that mouse temporarily infertile. It took a few more years of lab work to ultimately prove the concept, and in 2023, we published the in vivo proof demonstrating that we could use acute-acting sAC inhibitors to cause on-demand contraception in male mice.