17β-HSD1

Standard endometriosis treatment includes anti-inflammatory drugs, then hormone therapy that circulates throughout the body. Forendo Pharma is developing a new approach that offers a potentially more targeted treatment. The company’s endometriosis drug is still experimental, but Merck spinout Organon sees enough promise to acquire the startup outright. Organon announced Thursday that it will pay $75 million up front and assume about $9 million of Forendo’s debt. The Jersey City, New Jersey-based company has also agreed to development and regulatory milestone payments that could reach $270 million. If the endometriosis drug reaches the market, commercialization milestones could bring $600 million more. The Forendo acquisition agreement is Organon’s third women’s health deal since it spun out of Merck in June. Endometriosis is a condition in which the uterine lining, called the endometrium, grows outside of the uterus and causes pain and fertility problems. Turku, Finland-based Forendo aims to treat endometriosis by interfering with the abnormal growth of endometrial cells. The company’s drug, FOR-6219, is a small molecule designed to target an enzyme called hydroxysteroid 17-beta dehydrogenase type 1 (HSD17B1). Doing so inhibits the conversion of the hormone estrone into a highly potent form of estradiol, another hormone that regulates the growth of endometriotic tissue. Most endocrinology treatments focus on affecting hormones circulating throughout the body. According to Forendo, its drug is different than currently available treatments because of its local effect, working in the targeted tissues without affecting hormones circulating systemically. Forendo calls its approach “intracinology.” According to Organon and Forendo, the targeted effect of FOR-6219 means it could be studied as a long-term treatment for endometriosis. The drug is being readied for Phase 2 testing. The Forendo pipeline also includes a drug candidate for polycystic ovarian syndrome, which is associated with metabolic disorders, hyperandrogenism, and infertility. The condition has no FDA-approved treatment. Forendo’s experimental drug, a targeted therapy designed to block the enzyme HSD17B5, is preclinical. Organon is comprised of the former women’s health business and off-patent drugs of Merck. The pharmaceutical giant announced last year that it would place those drugs in a new business that would be spun out as a standalone, publicly traded company. The spinoff was completed in June. At that time, Organon closed its $215 million acquisition of Alydia Health, a startup that had commercialized a medical device for treating postpartum hemorrhage. In July, Organon licensed global rights to ebopiprant, a potential treatment for pre-term labor that is currently in mid-stage clinical development. Organon expects to close the Forendo transaction next month. The deal was announced just prior to Organon’s release of its financial results for the third quarter, the company’s first full quarter as a standalone company. Of Organon’s total $1.6 billion in third quarter revenue, women’s health accounted for $381 million. Organon’s profit for the period was $323 million. Photo by Flickr user Ed Uthman via a Creative Commons license

STOCKHOLM, SWEDEN – March 3, 2021. Karolinska Development AB (Nasdaq Stockholm: KDEV) announces today that its portfolio company, Forendo Pharma, has successfully completed a Phase 1 program for FOR-6219 – a candidate drug aimed for the treatment of endometriosis. Based on the positive results generated in this program, Forendo Pharma is now preparing a Phase 2 study in the US. The randomized, double-blind, placebo-controlled Phase 1 program of FOR-6219 included 66 healthy pre- and postmenopausal women. In the Phase 1a part of the study, single and multiple doses of the candidate drug were found to be safe and well tolerated. All primary endpoints of the study were met, and no serious adverse events were recorded. The pharmacokinetics of FOR-6219 were dose-proportional and a steady state was reached within 3 days, with the observed half-life of 16-18 hours offering the potential for once-daily dosing. In the Phase 1b part of the study, FOR-6219 was given to 36 premenopausal healthy women for 14 days during the proliferative phase of the menstrual cycle, to expand the safety data and explore secondary outcome measures. The premenstrual women under treatment experienced a continued normal ovulatory menstrual cycle. The positive data will be valuable in the design of subsequent clinical studies in endometriosis patients. “Current therapies for endometriosis are struggling to be widely adopted due to their side effects. Hence, the positive safety profile for Forendo Pharmas candidate drug FOR-6219 that has been documented in the Phase 1 program, together with the favorable pharmacokinetic profile, provides a compelling platform for its continued clinical development,” comments Karolinska Development's CEO, Viktor Drvota. Endometriosis is an estrogen-dependent disease that affects approximately 10 percent of all fertile women and is caused by cells that normally grow inside the uterus spreading outside the uterus, leading to chronic inflammation in the surrounding tissue. The disease manifests itself in many different ways and often causes very painful menstruation and chronic abdominal pain. Today's drug treatments alleviate the symptoms by inhibiting the body's estrogen synthesis. A clear disadvantage of this type of treatment is that it disturbs the systemic estrogen balance, which gives rise to osteoporosis and other serious side effects that complicate long-term medication. Forendo’s novel oral HSD17B1 inhibitor, FOR-6219, aims to reduce estrogen production locally in the endometriosis lesions, a key differentiator from competing endometriosis therapies. Karolinska Development's ownership in Forendo Pharma amounts to 10%. For further information, please contact: Viktor Drvota, CEO, Karolinska Development AB Phone: +46 73 982 52 02, e-mail: viktor.drvota@karolinskadevelopment.com Johan Dighed, General Counsel, Karolinska Development AB Phone: +46 70 207 48 26, e-mail: johan.dighed@karolinskadevelopment.com TO THE EDITORS About Karolinska Development AB Karolinska Development AB (Nasdaq Stockholm: KDEV) is a Nordic life sciences investment company. The company focuses on identifying breakthrough medical innovations in the Nordic region that are developed by entrepreneurs and leadership teams. The Company invests in the creation and growth of companies that advance these assets into commercial products that are designed to make a difference to patients' lives while providing an attractive return on investment to shareholders. Karolinska Development has access to world-class medical innovations at the Karolinska Institutet and other leading universities and research institutes in the Nordic region. The Company aims to build companies around scientists who are leaders in their fields, supported by experienced management teams and advisers, and co-funded by specialist international investors, to provide the greatest chance of success. Karolinska Development has a portfolio of ten companies targeting opportunities in innovative treatment for life-threatening or serious debilitating diseases. The Company is led by an entrepreneurial team of investment professionals with a proven track record as company builders and with access to a strong global network. For more information, please visit Attachment