Radius is a science-driven biopharmaceutical company that is committed to developing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases. Radius’ lead product candidate, the investigational drug abaloparatide for subcutaneous injection, has completed Phase 3 development for potential use in the treatment of postmenopausal women with osteoporosis. Radius’ Marketing Authorisation Application (MAA) for abaloparatide-SC for the treatment of postmenopausal women with osteoporosis is under regulatory review in Europe and a New Drug Application (NDA) is under regulatory review in the US by the Food and Drug Administration, with a Prescription Drug User Fee Act (PDUFA) date of June 30, 2017.
The Radius clinical pipeline also includes an investigational abaloparatide transdermal patch for potential use in postmenopausal women with osteoporosis and the investigational drug RAD1901 for potential use in the treatment of hormone-driven and/or hormone-resistant breast cancer, as well as for potential use in the treatment of vasomotor symptoms in postmenopausal women. Radius’ preclinical pipeline includes RAD140, a non-steroidal, selective androgen receptor modulator (SARM) under investigation for potential use in the treatment of breast cancer.
Our Investigational Product Candidates
The following table identifies the investigational product candidates in our current product portfolio, their proposed indication and stage of development:
Investigational drug product candidate abaloparatide-SC
Abaloparatide-SC has completed Phase 3 development for potential use as a subcutaneous injection for the treatment of postmenopausal women with osteoporosis. We hold worldwide commercialization rights to abaloparatide-SC, except for Japan. In December 2014, we announced the 18-month top-line data from our Phase 3 ACTIVE clinical trial, in which abaloparatide-SC met the primary endpoint with a statistically significant reduction in new vertebral fractures versus placebo, and in June 2015, we announced the top-line data from the first six months of the ACTIVExtend clinical trial and the 25-month combined data from ACTIVE and ACTIVExtend. Radius’ NDA for abaloparatide-SC is currently under review by the US Food and Drug Administration with a Prescription Drug User Fee Act (PDUFA) date of June 30, 2017. Radius’ MAA for abaloparatide-SC is currently undergoing regulatory review in Europe by the Committee for Medicinal Products for Human Use (CHMP).
Investigational drug product candidate abaloparatide-TD
We are also developing abaloparatide-transdermal, which we refer to as abaloparatide-TD, based on 3M’s patented Microstructured Transdermal System technology for potential use as a short wear-time transdermal patch. We hold worldwide commercialization rights to the abaloparatide-TD technology. During 2014, we reported progress towards the development of an optimized transdermal patch that may be capable of demonstrating comparability to abaloparatide-SC. In preliminary, nonhuman primate pharmacokinetic studies, we achieved a desirable pharmacokinetic profile, with comparable AUC, Cmax, Tmax and T1/2 relative to abaloparatide-SC. We believe that these results support continued clinical development of abaloparatide-TD toward future global regulatory submissions as a potential post-approval line extension of the investigational drug abaloparatide-SC. We commenced a human replicative clinical evaluation of the optimized abaloparatide-TD patch in December 2015, with the goal of achieving comparability to abaloparatide-SC, which we expect to complete during 2016.
Investigational drug product candidate RAD1901
RAD1901 is a selective estrogen receptor degrader, or SERD, that at high doses has potential for use as an oral non-steroidal treatment for hormone-driven, or hormone-resistant, breast cancer. RAD1901 is currently being investigated in postmenopausal women with advanced estrogen receptor positive, or ER-positive, HER2-negative breast cancer, the most common form of the disease. The compound is being investigated for use as a single agent or in combination with other therapies to overcome endocrine resistance in breast cancer.
In September 2015, we announced results from a Phase 1 maximum tolerated dose, or MTD, study of RAD1901 in 52 healthy volunteers. In the study, RAD1901 was administered to healthy postmenopausal women in doses ranging from 200mg to 1000mg, and the data showed that the tolerability of RAD1901 and the overall safety profile was supportive of continued development. In addition, a subset of subjects that received 18F estradiol positron emission tomography, or FES-PET, imaging demonstrated suppression of the FES-PET signal to background levels after six days of dosing.
In December 2014, we commenced a Phase 1, multicenter, open-label, two-part, dose-escalation study of RAD1901 in postmenopausal women with advanced ER-positive and HER2-negative breast cancer in the United States to determine the recommended dose for a Phase 2 clinical trial and to make a preliminary evaluation of the potential anti-tumor effect of RAD1901. Part A was initiated to evaluate escalating doses of RAD1901, and the Part B expansion cohort was initiated in March 2016 to allow for an evaluation of additional safety, tolerability and preliminary efficacy. No dose limiting toxicities have been reported to date.
In December 2015, we commenced a Phase 1 FES-PET study in patients with metastatic breast cancer in the European Union which includes the use of FES-PET imaging to assess estrogen receptor occupancy in tumor lesions following RAD1901 treatment.
In July 2015, we announced that early but promising preclinical data showed that our investigational drug RAD1901, in combination with Pfizer’s palbociclib, a cyclin-dependent kinase, or CDK, 4/6 inhibitor, or Novartis’ everolimus, an mTOR inhibitor, was effective in shrinking tumors. In patient-derived xenograft, or PDx, breast cancer models with either wild type or mutant ESR1, treatment with RAD1901 resulted in marked tumor growth inhibition, and the combination of RAD1901 with either agent, palbociclib or everolimus, showed anti-tumor activity that was significantly greater than either agent alone. We believe that this preclinical data suggests that RAD1901 has the potential to overcome endocrine resistance and has a profile that is well suited for use in combination therapy.
In January 2016, we entered into a worldwide clinical collaboration with Novartis Pharmaceuticals to evaluate the safety and efficacy of combining RAD1901, with Novartis’ investigational agent LEE011 (ribociclib), a CDK 4/6 inhibitor, and BYL719 (alpelisib), an investigational phosphoinositide 3-kinase inhibitor.
The clinical significance of these initial findings must be investigated in subsequent clinical trials, and all the resulting data are subject to regulatory review.
Investigational drug product candidate RAD1901
RAD1901 is also being evaluated at low doses as an estrogen receptor ligand for the potential reduction in the frequency and severity of moderate to severe hot flashes in postmenopausal women with vasomotor symptoms. We commenced a Phase 2b clinical study of RAD1901 for the potential treatment of postmenopausal vasomotor symptoms in December 2015.
Investigational drug product candidate RAD140
RAD140 is a potent, orally bioavailable non-steroidal selective androgen receptor modulator, or SARM, that resulted from an internal drug discovery program focused on the androgen receptor pathway, which is highly expressed in many ER-positive and ER-negative breast cancers. Due to its receptor and tissue selectivity, potency and long half-life, RAD140 could have clinical potential in the treatment of breast cancer where androgen modulation may offer therapeutic benefit.