In a strong day for biotech fundraising, Myovant Sciences Ltd. scored the biggest IPO of the year, pulling down $217.5 million, and Unity Biotechnology Inc. garnered a satisfying $116 million series B round.

Myovant CEO Lynn Seely told BioWorld Today that her firm's phase III-ready lead compound relugolix, "a beautiful case of a hormonal pathway that's very well understood," is set to enter experiments in male and female disorders.

Hamilton, Bermuda-based Myovant's oral, once-daily gonadotropin-releasing hormone receptor antagonist, relugolix – potentially a small-molecule drug pipeline unto itself, Seely said – will be tested in women with heavy menstrual bleeding associated with uterine fibroids, in women with endometriosis-associated pain and in men with advanced prostate cancer. "We know how it works," she said.

Myovant sold 14.5 million shares at $15 each, granting underwriters a 30-day option to purchase up to about 2.1 million more shares. The stock (NYSE:MYOV) closed Thursday at $13.26.

In June, Osaka, Japan-based Takeda Pharmaceutical Co. Ltd. and Bermuda's Roivant Sciences Ltd. formed Myovant around relugolix and another compound, RVT-602 to treat female infertility as part of assisted reproduction. RVT-602, a peptide analogue of kisspeptin, has gone as far as phase II in men's health indications, and Myovant aims to run phase I pharmacokinetic and pharmacodynamic studies next year, said Seely, who spent a decade as the chief medical officer at San Francisco-based Medivation Inc., where she led the development of prostate cancer drug Xtandi (enzalutamide). The compound pulled in sales of $1.9 billion in 2015 and drew a $14 billion acquisition by Pfizer Inc., of New York. Myovant filed for the IPO about a month ago. (See BioWorld Today, Aug. 23, 2016, and Oct. 4, 2016.)

Cash from the upsized IPO will get Myovant through the phase III results to "at least early 2019 and beyond," Seely said, adding that the women's health zone has been "really ignored by big pharma over the last two decades," which left patients to surgical solutions. Her firm wants to create easier relief – and potentially big revenues. "I think people are really starting to appreciate that there's a lot of open space here," she said.

Two phase III studies will begin the first quarter of next year, with endometriosis trials soon to follow, she said. "Some people have been focusing on the fact that we only have nine employees" at Myovant, she said, but the parent company, Roivant, brings to bear on the effort "a significant development arm," and Myovant is building its presence in the San Francisco area. Another Roivant-launched firm, Axovant Sciences Ltd., reaped $360 million in an IPO last year. (See BioWorld Today, May 13, 2015.)

Pfizer and BB Biotech AG, of Kusnacht, Switzerland, each invested $30 million in Myovant. For its money, Pfizer got a board observer seat and right of first negotiation on the two compounds, though "it's important to note that any incoming interest is not part of that deal," Seely said.

Citigroup Global Markets Inc., Cowen and Co. LLC, Evercore Group LLC and Barclays Capital Inc. are acting as joint book-running managers for IPO, with JMP Securities LLC serving as lead manager and Robert W. Baird & Co. Inc. as co-manager.

Meanwhile, with its series B, San Francisco-based Unity is appointing as CEO Keith Leonard, 25-year biotech industry veteran and current executive chairman. Leonard was most recently CEO of Kythera Biopharmaceuticals Inc., acquired by Allergan plc in late 2015 for $2.1 billion. He founded Kythera with Unity founder (and previous CEO of Unity) Nathaniel David, who will become the company's president. (See BioWorld Today, June 8, 2015.)

David explained the rationale behind the firm, telling BioWorld Today that "when you're conceived as a single cell, over the arc of your life, that cell will divide perhaps as many as 50 times, and when that cell encounters stress, whether it's lots of cell division or some other form of stress, [it] can adopt this state called cellular senescence. It stops dividing forever, and begins secreting all sorts of factors that turn out to drive multiple diseases of aging. After you're about 30 years old, these cells accumulate in your body more and more every year, contributing to more chronic inflammation," known to underlie many diseases of aging, he said.

Unity has developed strains of mice that model natural aging as well as disease states, and then cleared the senescent cells to see what happened. The mice "not only live 35 percent longer on average, but the most important thing is this extended thing we call the health span, which is the duration of time these animals live without chronic diseases of aging," David said. Such knowledge may be useful against disorders "viewed heretofore as unescapable aspects of being old," he said.

But will the mouse research translate? "I think our most important audience for data is actually ourselves – convincing ourselves that what we're doing is smart and is not going to fail when we go into the clinic," he said. Unity also has tried its approach in human knee cartilage donated by sick people who were having their knees replaced. "We can cause that knee to start growing cartilage again by soaking it in one of our drug molecules," he said, thereby providing more support for the approach. He said he has a "pretty high conviction that we're going to find places in which the animal models do in fact reflect human disease." Clearing senescent cells was found to have 21 different effects thus far.

'most druggable' target in aging

The series B features new investments from longtime life science investors Arch Venture Partners, Baillie Gifford, Fidelity Management and Research Company, Partner Fund Management and Venrock. Other investors include Bezos Expeditions and existing investors Wuxi Pharmatech and Mayo Clinic Ventures. This spring, Unity and Ascentage Pharma Group, of Taizhou, Zhejiang, a clinical-stage firm focused on apoptosis-targeted oncology drug discovery and development, entered a deal whereby Unity gained access to Ascentage's library of small-molecule compounds targeting programmed cell death. (See BioWorld Today, April 28, 2016.)

Unity CEO Leonard told BioWorld Today that David "has had the company in stealth mode for coming up on five years," and the firm has now reached an "inflection point where we're going to be preparing to submit INDs to the FDA" while continuing to validate the science. "This is not going to be a quick endeavor," he said, and will require patience. "The group [of investors] we've assembled reflects that very specifically," he said, though "they see the promise of the biology and the size of the potential markets." Along with osteoarthritis of the knee, Unity will first move to the clinic with a possible glaucoma therapy.

The journal Science Thursday published research that further demonstrates Unity's thesis: the central role of senescent cells in disease. Written by Unity co-founders Judith Campisi and Jan van Deursen, it describes the key role of senescent cells in atherosclerotic disease and shows that the selective elimination of them holds the promise of treating atherosclerosis in humans. In animal models of early and late disease, the authors prove that selective elimination of senescent cells inhibits the growth of atherosclerotic plaque, reduces inflammation and alters the structural characteristics of plaque so that higher-risk "unstable" lesions take on the structural features of lower-risk "stable" lesions.

Previous papers during the past year in Nature Medicine and Nature also helped make the case, David said, but the latest one shows Unity's method can "actually cause mature disease to go backward, taking the health span observation and narrowing it to something all of us can get our heads around. Gradually, pieces of the puzzle have fallen into place."

Unity's main competitor in the space is Calico, aka California Life Sciences LLC, he said. In 2014, Chicago-based Abbvie Inc. and Calico agreed to pour up to $750 million each into a discovery and development collaboration devoted to advancing neurodegeneration and cancer therapies through phase IIa and beyond. The companies will each provide up to $250 million to fund the collaboration at first. Calico will carry out R&D work for the first five years, with Abbvie providing support and an equal share of program costs under terms of the agreement. (See BioWorld Today, Sept. 5, 2014.)

"A lot of our competition has been around recruiting the best people, because we go after similar candidates, but I think we've done very well against Calico in that regard," David said. Otherwise, at this stage, characterizing the landscape is difficult. It's dotted with "smaller companies, but they're not heavily capitalized," he said.

"Cellular senescence is not the only reason you age," David said, but findings show that mice age "differently and more slowly" when such cells are cleared. "There might ultimately be, say, six of these mechanisms that collectively work together to create the thing we call aging," but senescent cells represent "absolutely the most druggable of these mechanisms that we're aware of today," he said. The work could lead to therapies given intermittently – once every six months or even once every three years.