The Population Council, Inc.

A reversible male contraceptive could be a lot closer to reality than you think. Earlier this summer, doctors were tantalized by preliminary data showing that an experimental drug safely reduced sperm count. But several questions remained unanswered, including how effective the drug was at preventing pregnancies and how it would be commercialized. Now, a small biotech startup that wasn’t involved in the NIH-funded study is providing some answers. Charlottesville, VA-based Contraline won the exclusive rights to finish developing and commercializing the new hormone-based drug, the company exclusively told Endpoints News . The data from the Phase 2 study are still being analyzed and are set to be written up for publication later this year. But CEO Kevin Eisenfrats said in an interview that so far the drug looks more than 99% efficacious at preventing pregnancies. If that number holds, it would rank the drug among the most effective birth control options . IUDs and vasectomies are also more than 99% effective, while female birth control pills are about 93% effective and condoms are only 87% effective. “When I saw the interim data, I was so blown away. I thought, ‘We need to own this product,’” Eisenfrats said. “This is something I want to take. This is something my friends are going to take. This is something that’s going to change the world.” But the effectiveness of the drug will depend on people using it properly. The drug, called NES/T, is made of two hormones — nestorone and testosterone — formulated in a gel that’s rubbed on the shoulders daily. It takes an average of 8 weeks to start working, though it can take longer for some people. Diana Blithe, who helms contraceptive research at the National Institutes of Health, led the Phase 2 trial and presented the sperm count data at the Endocrine Society’s annual meeting in June. She told Endpoints in an email that the study was still ongoing and could not confirm the drug’s 99% efficacy. The study was scheduled to wrap up in July, and Eisenfrats said the efficacy phase of the trial is complete. He plans to start a Phase 3 study of about 400 couples next summer, and if all goes well, submit the drug for approval in 2028. It could become the first pharmaceutical birth control option for men, providing a long-overdue alternative to condoms and vasectomies. NES/T was developed by the Population Council, a nonprofit behind the early development of several birth control products, including the copper IUD and the abortion pill mifepristone . The NIH funded the recent clinical trial of NES/T and might help with the Phase 3 as well, according to Eisenfrats. But neither group takes drugs all the way to the market. Earlier this year, the Population Council began looking for a drug company to carry the torch. At first glance, Contraline might not seem an obvious choice. The 18-person startup has never taken a drug into advanced clinical studies and will need to raise significant funding in order to do so. Eisenfrats estimates that the Phase 3 trial will cost about $50 million, and he’s looking to raise at least $65 million in Series B funding for studies of NES/T and an injectable male contraceptive that Contraline is also developing. Despite that, the startup beat bigger and more experienced companies for the rights to a global exclusive license to NES/T, according to Eisenfrats. James Sailer, co-president of the Population Council and head of its biomedical research center, told Endpoints that the nonprofit is confident that Contraline will be able to raise the needed funds. He was more worried about the drug getting lost during a pipeline reprioritization at a bigger company or after an acquisition of a medium-sized company. “We’ve seen this many times,” Sailer said. There’s a lingering stereotype that men aren’t interested in new contraceptives, but Sailer said that data over the past 20 years have repeatedly, and increasingly, shown this isn’t true. “There are still people who don’t believe it,” he said. “But Contraline does believe it. They have looked carefully at the data and Kevin — he’s a true believer.” Eisenfrats has been obsessed with the idea of male contraception his entire adult life and pointed to the MTV show “16 and Pregnant” as a source of inspiration in his college admissions essay. “There were so many unintended pregnancies, and it just felt like the answer to that was better male methods,” Eisenfrats said. In 2015, just as he was wrapping up his bachelor’s degree in nanomedicine engineering and chemistry at UVA, he co-founded Contraline. In the nine years since Eisenfrats has been working on a hydrogel that’s injected into the vas deferens to block the ducts and prevent sperm from being transported out of the testes. Unlike vasectomies, which cut and tie these tubes, Contraline’s approach, dubbed ADAM, is designed to be easily reversible with a second injection that dissolves the hydrogel. The method, which Eisenfrats calls “the IUD for men,” is currently being tested in a 60-person safety study in Australia, with a Phase 2 trial planned for next year. Until Eisenfrats saw the NES/T data this summer, he never imagined that Contraline would also develop a hormonal contraceptive for men. The hormonal approach got a bad rap in 2016. In a study run by the World Health Organization, scientists injected progestins, synthetic versions of hormones that suppress sperm production, and testosterone in men every 8 weeks. Although the drug showed signs of working, the study was cut short due to frequent side effects, including acne and mood disorders. NES/T aims to overcome those problems by using a safer sperm-reducing progestin called nestorone — previously developed by the Population Council as a female contraceptive for the vaginal birth control ring Annovera — and striking a better balance of that molecule and testosterone, which is needed to maintain baseline levels of the hormone. “I always thought the side effects would make this a non-tolerable, non-useable product,” Eisenfrats said. But in the Phase 2 study, the most common side effects were mild acne and increased libido, he added. The drug might not have to completely stop sperm production to be effective. Having fewer than 15 million sperm per milliliter of semen is considered low. In the Phase 2 trial, having 1 million sperm per milliliter was the threshold for contraception. Half the men in the study, which enrolled 460 couples, hit this benchmark after 8 weeks, and 86% reached it after 15 weeks. Once sperm levels were low enough, the couples stopped using other forms of birth control for a year. The efficacy results have yet to be formally reported, but according to Eisenfrats, “it was better than 99% efficacy, which is virtually unheard of.” That efficacy figure also appears in the company’s investor presentation, which was shared with Endpoints, but it is unclear if the number includes the 14% of participants who hadn’t had their sperm suppressed by 15 weeks. The slide deck also mentions that “100% of patients recovered sperm counts and hormone levels” during a 24-week recovery period at the end of the study, but again it’s unclear if this number discludes some trial participants. Eisenfrats was reluctant to disclose details about the design of the Phase 3 trial because the NIH is still waiting on guidance from regulators. But he hopes that the study will be “similar and confirmatory” to the Phase 2 design since the two hormones in NES/T are already approved drugs on their own. Finding volunteers for the study shouldn’t be a problem. Contraline has a database of nearly 10,000 men, mostly aged 20 to 40, who are on a waitlist to be part of the company’s clinical trials. “We get emails every week from random guys,” Eisenfrats said. “We have done zero advertising of that.” Now the company must find funding to put NES/T through its final test. Contraline disclosed a $10.7 million Series A financing in 2021, but Eisenfrats said he’s raised about $30 million total since the company’s inception, including from investors at the Founders Fund, GV and MBX Capital. Eisenfrats is courting biotech-focused venture capital firms for the first time, pitching peak sales of NES/T between $1 billion and $2 billion in the US, assuming prescriptions cost $50 to $65 a month and are sold through telehealth companies like Hims or Ro. Sailer said that Contraline’s license to NES/T is contingent on the startup’s ability to raise money. If the startup fails, the Population Council will get the drug back. But if the Contraline and the drug are successful, the nonprofit will get royalties on future sales, and the NIH will get a cut, too. Eisenfrats and Sailer both declined to disclose further financial details. “They believe that the market is there, and they are very, very determined to be successful,” Sailer said. “And they understand that it’s going to take some trailblazing.” Editor’s note: This story was corrected. It previously misidentified the headquarters of Contraline.

YCT-529 is the first contraceptive of its kind to be tested in humans. Women have long shouldered the burden of birth control. Now, men may soon have an option that is not only hormone-free, but also allows space between doses.  YourChoice Therapeutics on June 4 at the BIO International Conference in San Diego will share phase 1a data on 16 subjects showing that doses of their drug YCT-529 are safe for men. The figures also hinted at the possibility that the drug’s half-life might make it possible to spread doses out by as much as two weeks—an attractive idea given that some in the industry have expressed doubt that men would be willing to take daily pills, co-founder Akash Bakshi told Fierce Biotech Research. “I think one clear ‘aha moment’ for us is that we might have an extended half-life at each dose, that compliance might not necessarily be an issue,” he said. “Therefore, this is something that improves the health and well-being of women, too.” Bakshi and Nadja Mannowetz, Ph.D., started YourChoice in 2018 with the goal of giving women a hormone-free way to prevent pregnancy. After licensing a drug called niclosamide from the University of Minnesota, they shopped their idea around to investors to get it off the ground. But there was little interest.  Then the pandemic hit—and niclosamide, which also happened to have antiviral activity, turned out to be a better fit for COVID-19 than contraception, at least in the eyes of would-be financiers. They repackaged it under a spinout, ANA Therapeutics.  “[ANA] outraised the contraceptive company four-fold in less than three weeks,” Bakshi recalled. “It was the same team, the same drug, just a different indication.” ANA was acquired by NeuroBo Pharmaceuticals in 2020, leaving Bakshi and Mannowetz back where they started. Given how challenging it was to raise money for a new contraceptive for women, they decided to pivot to a different solution: a nonhormonal, reversible, oral contraceptive for men developed by the same University of Minnesota scientist who’d created niclosamide, Gunda Georg, Ph.D. It's a busy time in the world of male contraceptive drugs, which after decades of development have begun to make serious strides in the clinic thanks to investments from institutions like the National Institutes of Health's Contraceptive Development Program and nonprofits like the Male Contraceptive Initiative. Just a day before YourChoice presented its data at BIO, Population Council researchers shared that a hormone-based male birth control gel called Nesterone was safe and effective in a 222-subject phase 2 trial.  Nesterone works like most birth control drugs under development for men: It reduces sperm production by altering testosterone levels. While an effective approach, adverse effects have stopped earlier trials of testosterone-based contraceptives before they make it to large-scale studies.   YCT-529, in contrast, doesn’t act on hormones at all. It blocks retinoic acid receptors in the testes that are involved in sperm production and thus has a lower likelihood of side effects.  “Men need more birth control options, and they need more than one … we won’t clearly know the advantages of hormone-free versus hormone-based options until we have large-scale clinical studies,” Bakshi said in a follow-up email to FBR. “What’s fundamental is that we deliver several new options for men. Women have borne the burden of hormonal birth control for too long." An opportunity for options   Though it's still too early to say whether YCT-529 has efficacy in humans, preclinical data in mice, dogs and primates showed that the drug was safe, up to 99% effective and reversible. YourChoice is now in the process of launching a phase 1b trial, which will look at the safety and pharmacokinetics of multiple doses, and plans to complete it by early 2025.  The company has enough runway to get through 2026, which takes YCT-529  through early safety studies and perhaps initial efficacy tests as well, according to Bakshi. The team in 2022 closed a $15 million series A led by Future Ventures. New funds raised will be spent on commercializing the drug.  They might also go toward Bakshi and Mannowetz’s original vision of a non-hormonal female contraceptive. Though YCT-529 does ultimately help ameliorate the problem they set out to solve, there’s enough room in the market for both, Bakshi said. If successful, the drug might even drum up interest in non-hormonal female birth control.  “I think male contraception seems to be one mechanism to suggest to the market that this is an opportunity by which we can change the contraceptive landscape,” he said. “And I hope it also poses a question: If men get a non-hormonal pill before women do it, where's the hormone-free pill for women?” Editor's note: YourChoice first presented its data at BIO, not at the Endocrine Society's meeting as an earlier version of this article stated. 

Celanese VitalDose® Drug Delivery Platform Will Enable the Population Council’s Contraceptive and HIV Multipurpose Prevention Technology DALLAS--(BUSINESS WIRE)-- Celanese Corporation (NYSE: CE), a global specialty materials and chemical company, today announced that it has entered into an agreement with the Population Council to supply its VitalDose® Drug Delivery Platform for use in a new Multipurpose Prevention Technology (MPT) Intravaginal Ring (IVR). The IVR is being developed to provide both contraception and protection against HIV and is currently in a phase 1b clinical trial. Long-acting continuous drug delivery dose forms, like IVRs, offer fewer barriers to reliable use than oral forms requiring daily doses. Providing benefits for patients, like enhanced convenience, can lead to better outcomes and is the driver for developing patient-centric dose forms. The VitalDose Drug Delivery Platform has been used in patient-centric dose forms in women’s health for over two decades, offering tunable and consistent elution for a variety of active pharmaceutical ingredient (API) molecules. “Our data indicate that women overwhelmingly prefer, and are more likely to use, a multipurpose prevention product that prevents pregnancy and sexually transmitted infection acquisition over a product that prevents only one of the two,” said Bríd Devlin, Chief Scientific Officer of Product Development at the Population Council. “This IVR would address the need for a contraceptive solution while also providing preventive therapy against HIV at a time when 63 percent of new HIV infections are contracted by women and girls.” “There is an undeniable need for new patient-centric technologies that provide women with new healthcare options and address the overlapping global burdens of unintended pregnancy and HIV,” said Susan Rahe, Vice President of Pharmaceutical Solutions at Celanese. “Our team recognizes the benefits of a sustained release dose form to further the work of Population Council as they continue to develop global treatments to benefit the lives of patients.” The VitalDose Drug Delivery Platform provides reliable, controlled-release performance for a wide range of molecule types and has a long history of use in approved parenteral drug products in the United States, Europe and many other geographies. For more information on Celanese VitalDose technology, visit . About Celanese Celanese Corporation is a global chemical leader in the production of differentiated chemistry solutions and specialty materials used in most major industries and consumer applications. Our businesses use the full breadth of Celanese's global chemistry, technology and commercial expertise to create value for our customers, employees, shareholders and the corporation. As we partner with our customers to solve their most critical business needs, we strive to make a positive impact on our communities and the world through The Celanese Foundation. Based in Dallas, Celanese employs approximately 13,000 employees worldwide and had 2022 net sales of $9.7 billion. For more information about Celanese Corporation and its product offerings, visit . About the Population Council The Population Council is a leading research organization dedicated to building an equitable and sustainable world that enhances the health and well-being of current and future generations. We generate ideas, produce evidence, and design solutions to improve the lives of underserved populations around the world. Learn more at . View source version on businesswire.com: Contacts Celanese Contacts: Investor Relations Brandon Ayache Phone: +1 972 443 8509 brandon.ayache@celanese.com Media Relations – Global Brian Bianco Phone: +1 972 443 4400 media@celanese.com Media Relations Europe (Germany) Petra Czugler Phone: +49 69 45009 1206 petra.czugler@celanese.com Population Council Contacts: Media Inquiries pubinfo@popcouncil.org Visit our Media section Partnerships development@popcouncil.org Product licensing opportunities Anita Garg agarg@popcouncil.org Source: Celanese Corporation View this news release online at: