On June 06, 2016 Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP) (Cyclacel or the Company), reported updated Phase 1 data from its DNA damage response program evaluating a combination regimen of two Cyclacel product candidates, seliciclib, a cyclin dependent kinase (CDK) inhibitor, and sapacitabine, a nucleoside analogue (Press release, Cyclacel, JUN 6, 2016, View Source [SID:1234513037]). The regimen was orally-administered as sequential (Part 1) or concomitant (Part 2) treatment to 67 heavily-pretreated patients with advanced solid tumors. Antitumor activity was demonstrated in a subgroup of 45 patients with breast, ovarian and pancreatic cancers who tested positive for BRCA mutations (44 germline and 1 sporadic) with a 35.6% disease control rate (1 CR, 5 PR and 10 SD). Treatment durations in responders ranged between 16 and over 240 weeks. No CR or PR was observed in BRCA negative patients. Data were presented at an oral presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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"We are encouraged by the durable responses and stable disease seen with the seliciclib and sapacitabine combination in patients with BRCA mutations, in particular because most were heavily pretreated and many are able to remain on study for extended periods," said Sara M. Tolaney, M.D., M.P.H., Associate Director, Clinical Research, Breast Oncology, Dana-Farber Cancer Institute, Boston. "Our findings from Parts 1 and 2 of the study have shown that the orally-administered regimen is well tolerated with manageable toxicities. Based on the results, we believe that further clinical evaluation of this combination regimen is warranted. A Part 3 extension of the study is currently enrolling advanced breast cancer patients with BRCA mutations."

"The findings reported in Dr. Tolaney’s presentation show that the combination treatment of seliciclib and sapacitabine is active and tolerable," said Judy Chiao, M.D., Vice President, Clinical Development and Regulatory Affairs of Cyclacel. "This clinical observation may be directly related to the drugs interference with the capacity of BRCA-mutated cancer cells to repair and survive sapacitabine-induced breaks in their DNA. If these preliminary findings are confirmed by further data, this regimen may provide an important treatment option for patients with BRCA-mutated cancers."

"The ASCO (Free ASCO Whitepaper) data build on earlier data from our DNA damage response program highlighted by the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting Program Committee in a 2013 press conference," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "The updated data support and extend clinical evidence of efficacy with different schedules of the combination in this patient population. We are encouraged with the durability of responses and stable disease, with ongoing responding patients achieving treatment durations exceeding 1 and 4.5 years respectively. We look forward to reporting data from the ongoing Part 3 extension in BRCA positive patients with breast cancer and increasing our understanding of the potential benefits of this differentiated treatment strategy in a targeted patient population with significant unmet medical need."

Results

The trial is a dose escalation study conducted in patients with advanced and incurable solid tumors. The orally-administered regimen consists of sapacitabine administered twice daily for 7 days sequentially followed by seliciclib twice daily for 3 days over a 21 day cycle (Part 1, n=38); and sapacitabine dosed each morning followed by seliciclib each evening, each once daily for 5 days per week for 2 weeks of a 28 day cycle (Part 2, n=29). The primary objective of the trial is to determine the maximum tolerated dose with a secondary objective of antitumor activity of the combination. Sixty-seven patients have been treated in Parts 1 and 2 of the study, of which 44 were found to carry BRCA mutations and one a sporadic BRCA mutation.

Best Responses

PART 1 PART 2
BRCA carriers Others BRCA carriers Others
(n=16) (n=22) (n= 28) (n=1)
CR 1 - - -
PR 3 - 2 -
SD 2 6 7 1*
ORR (CR/PR) 25 % 0 % 7 % 0 %
Disease Control (CR/PR/SD) 6 (37.5%) 6 (27.3%) 9 (32.1%) 1 (100.0 %)

* One patient had a sporadic BRCA mutation. CR=complete response, PR=partial response, SD=stable disease.

One CR and five PR were observed in BRCA mutation carriers with breast, ovarian and pancreatic cancers. Treatment durations for the 3 breast/ovarian cancer responders in Part 1 are 54, 93, over 240 weeks and the one breast cancer responder in Part 2 over 76 weeks respectively. Treatment durations for the two pancreatic cancer responders, one each in Parts 1 and 2, are 21 and 16 weeks respectively. Responders included patients who underwent prior treatment with PARP inhibitors and PARP naïve patients. SD was observed in 9 BRCA mutation carriers and 1 sporadic BRCA positive patient with treatment durations ranging from 16 to 88 weeks.

Overall in BRCA positive patients (Parts 1 and 2, n=45), disease control rate is 35.6% and overall response rate (ORR) is 11% (Part 1 ORR 25% and Part 2 7%). The difference in Part 1 and Part 2 ORRs may suggest that the seliciclib dose in the Part 2 schedule may be too low for enhancing the activity of sapacitabine.

Pharmacodynamic effects of the seliciclib and sapacitabine combination were observed in skin biopsies. Part 1 biopsies following treatment showed a 2.3-fold increase in DNA damage induced by sapacitabine, as measured by gamma-H2AX immunohistochemistry. Additional DNA damage occurred after treatment with seliciclib with a 0.58-fold further increase in gamma-H2AX staining.

In Part 1 recommended Phase 2 doses (RP2D) are: sapacitabine 50 mg b.i.d./seliciclib 800 mg b.i.d. Most frequent grade 3/4 adverse events were neutropenia (16%) and elevation in AST (16%). In Part 2 RP2D are: sapacitabine 250 mg q.d./seliciclib 200 mg q.d. Most frequent grade 3/4 adverse events were neutropenia (28%) and elevation in AST (10%). Dose limiting toxicities were reversible elevations in transaminase and bilirubin, neutropenia or febrile neutropenia and pneumonia.

Abstract: 2503
Title: Phase I study of sapacitabine and seliciclib in patients with advanced solid tumors
Date/Time: June 6, 2016 9:00 a.m. — 9:12 a.m. CDT
Location: E354b
Session Title: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Authors: SM Tolaney1, J Hilton1, JM Cleary1, L Gandhi1, EL Kwak1, JW Clark1, A Wolanski1, T Bell1, SJ Rodig3, JH Chiao2, D Blake2, G Shapiro1
1Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; 2 Cyclacel Ltd, Dundee, United Kingdom; 3 Brigham and Women’s Hospital, Boston, MA.

The abstract can be accessed through the ASCO (Free ASCO Whitepaper) website, View Source

About sapacitabine

Sapacitabine is an oral nucleoside analogue prodrug whose metabolite, CNDAC, generates single-strand DNA breaks (SSB), either leading to arrest of the cell cycle at G2 phase or development of double-strand DNA breaks (DSB). CNDAC-induced DSB repair is dependent on homologous recombination (HR). BRCA mutations in cancer cells are a cause of HR deficiency, making them susceptible to cell death induced by sapacitabine. Sapacitabine is the subject of SEAMLESS, a Phase 3 trial, which has completed enrollment and is being conducted under an SPA with the U.S. Food and Drug Administration (FDA) as front-line treatment for acute myeloid leukemia (AML) in the elderly. Sapacitabine has been evaluated to date in over 1000 patients including randomized Phase 2 and 3 trials in patients with hematological malignancies and previously treated solid tumors, including lung cancer.

About seliciclib

Seliciclib is an orally-available CDK inhibitor molecule that selectively inhibits enzyme targets, CDK2 and CDK9, which are central to the process of cell growth, survival and cell cycle control. Seliciclib treatment has been reported to inhibit the two major DNA double-strand break (DSB) repair pathways, homologous recombination (HR) and non-homologous end joining (NHEJ), by reducing expression of components of each pathway. It may potentiate the activity of sapacitabine by compromising HR protein expression and activation or by potentiating apoptosis following sapacitabine-induced DNA damage. Seliciclib has been evaluated to date in approximately 450 patients including randomized Phase 2 trials in patients with previously treated lung cancer and nasopharyngeal cancer.

On June 6, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported results from the final analysis of the Phase 1 study of MM-151, a novel investigational oligoclonal epidermal growth factor receptor (EGFR) inhibitor, in patients with refractory solid tumors (Press release, Merrimack, JUN 6, 2016, View Source [SID:1234513061]). These results were presented at a Poster Discussion Session at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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Data from the Phase 1 study show positive clinical activity across multiple solid tumor types in a heavily pretreated patient population. Twenty-one percent of evaluable patients in the metastatic colorectal cancer (CRC) cohort achieved an objective response and 54 percent of patients showed a decrease in tumor size. A median progression-free survival (PFS) of four months was also observed within the CRC cohort. MM-151 also exhibited positive clinical activity in both EGFR-treatment refractory and EGFR-treatment naïve populations. These preliminary data support the potential for broad clinical effect, and demonstrate an acceptable safety profile consistent with existing EGFR therapies.

"We are excited to present the final analysis of the Phase 1 data of MM-151, Merrimack’s novel oligoclonal EGFR-inhibitor," said J. Marc Pipas, M.D., Senior Medical Director at Merrimack. "The promising preliminary Phase 1 data highlights MM-151’s ability to impair EGFR-driven signaling and overcome resistance, particularly in colorectal cancer patients. We are encouraged by these results given the unmet needs in this patient population, and we look forward to further evaluating this investigational therapy’s potential to address this challenging disease."

CRC is the third most common cancer and is the second leading cause of cancer death in the United States. An estimated 144,000 new cases are expected to be diagnosed in 2016. The five-year survival rate for metastatic CRC is estimated at 11 percent.i The two most recent approved drugs for late stage metastatic CRC demonstrated objective response rates of less than two percent and PFS below two months in their clinical studies, while demonstrating an overall survival benefit versus best supportive care (no drug treatment)ii iii.

Methodology and Results

This study evaluated MM-151 as a monotherapy and in combination with irinotecan. An expansion cohort was enrolled to evaluate clinical activity in EGFR-refractory metastatic CRC patients. Subset analyses and additional biomarker evaluations were performed in EGFR-driven indications. A total of 111 patients were treated with escalating dose levels; 87 patients on monotherapy and 24 patients receiving MM-151 in combination with irinotecan. The most common tumor types were CRC (45 [41%]), head and neck cancers (14 [13%]) and non-small cell lung cancer (11 [10%]).

Safety of MM-151

MM-151 demonstrated a comparable safety profile to approved EGFR inhibitors as a monotherapy and in combination with irinotecan.
Apart from infusion reactions, which occurred at decreasing frequency and severity as the dosing schedule was modified over the course of the study, the most common adverse events reported were rash, hypomagnesemia, fatigue and diarrhea in the monotherapy cohorts. These adverse events were expected and consistent with EGFR inhibition class toxicities.
Results

Preliminary indications of clinical activity with MM-151, across both the EGFR-refractory and naïve populations, suggest there is potential for broad effect.
Biomarker profiling suggests MM-151 may overcome mechanisms of resistance.
Preliminary data in the CRC subset show 54 percent of evaluable patients had a reduction in tumors. Forty-five percent (13/29) of patients in the CRC subset achieved stable disease or partial response at three cycles of treatment and 17 percent (5/29) achieved a partial response, with highly durable responses and disease control.
Preliminary biomarker analysis of blood samples ("liquid biopsies") following MM-151 treatment show low occurrence of acquired KRAS/NRAS/BRAF mutations in the CRC cohort and no occurrence of acquired EGFR extracellular domain mutations, which have been reported to mediate resistance to cetuximab and panitumumab.
A median PFS of four months was observed in the CRC cohort.
Observations in exploratory biomarker analyses are consistent with the multiple mechanisms of action that have been previously described for MM-151 in preclinical studies, including EGFR downregulation, expression of high-affinity EGFR ligands across indications (including refractory metastatic CRC) and activity in tumors expressing EGFR and downstream mutations.
Further clinical evaluation is underway.
About MM-151

Merrimack used its systems biology approach to engineer MM-151, an oligoclonal therapeutic that is a mixture of three fully human monoclonal antibodies designed to bind and inhibit signaling of EGFR. EGFR-mediated signaling promotes the growth and survival of cancer cells and is recognized as an important drug target in several types of cancer, including colon, lung, breast, pancreatic and head and neck cancers. The use of three antibodies maximizes receptor inhibition, and provides mechanisms to overcome resistance to EGFR-targeted therapies. MM-151 is also being evaluated in two other Phase 1 studies; one in combination with the ONIVYDE (irinotecan liposome injection) regimen for metastatic CRC, and another in a first-of-its-kind, multi-arm basket study in combination with three other novel agents, two of which are from Merrimack’s oncology pipeline. Merrimack initiated these studies in May.

On June 06, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper), in Chicago, Illinois (Press release, Calithera Biosciences, JUN 6, 2016, View Source;p=RssLanding&cat=news&id=2175227 [SID:1234513016]). The data demonstrated the clinical activity, tolerability and unique mechanism of action of CB-839 in patients with renal cell carcinoma and triple negative breast cancer (TNBC).

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"CB-839 is the first tumor metabolism drug to target a pathway that starves cancer cells by directly depriving them of a key nutrient. The combination data presented at ASCO (Free ASCO Whitepaper) demonstrates that CB-839 can safely be added to standard of care therapeutics to treat solid tumors with the potential to improve clinical outcomes," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

CB-839 in Renal Cell Carcinoma

Dr. Funda Meric-Bernstam from MD Anderson Cancer Center will present a poster titled, "Phase I study of CB-839, a small molecule inhibitor of glutaminase, alone and in combination with everolimus in patients with renal cell carcinoma," (Abstract #4568). As of May 23, 2016, thirty-five renal cell carcinoma patients had been treated, including ten in combination with 10 mg daily everolimus, and twenty-five patients treated with CB-839 dosed as a monotherapy. In the combination group, the overall disease control rate was 80%, including one partial response; among eight clear cell and papillary patients, the disease control rate was 100%. The median time on study for these patients is currently 6.5+ months, exceeding the expected progression free survival of everolimus alone in this population. Time on treatment is currently equal to, or greater than the time on prior therapy for most patients, and seven of eight patients remain on study. The combination of CB-839 and everolimus has been well tolerated to date. There was one case of dose-limiting, grade 3 pruitic rash at the 400 mg dose level, which led to a reduction in the dose of everolimus for that patient. On the basis of this efficacy data, the company plans to continue development in combination therapy for renal cell carcinoma.

Among 21 efficacy evaluable patients treated as a monotherapy, 52% experienced stable disease or better, including one partial response. The monotherapy cohort represents an update from the data presented November 8, 2015 at the American Association of Cancer Research-NCI-EORTC conference.

CB-839 in Triple Negative Breast Cancer

Dr. Angela DeMichele from the University of Pennsylvania presented a poster titled, "Phase I study of CB-839, a small molecule inhibitor of glutaminase in combination with paclitaxel in patients with triple negative breast cancer," (Abstract #1011). The abstract was also selected for a poster discussion presentation on Sunday, June 5, 2016. Eligible patients include locally advanced/metastatic TNBC, refractory disease, with prior paclitaxel allowed. As of May 23, 2016, fifteen triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four. The majority of patients had received at least three prior lines of therapy. Six patients received five or more prior therapies in the advanced/metastatic setting. Most patients had received prior taxanes in either the neo-adjuvant (n=7) or metastatic (n=5) setting. Among patients treated with CB-839 doses of at least 600 mg bid (n=8), there were 3 partial responses (38%) and disease control (response or stable disease) in 7 patients (88%). Two of the partial responses were observed in patients that were refractory to paclitaxel in a prior course of therapy. The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been easily manageable and reversible, including several paclitaxel related toxicities. There was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient.

Investor Event and Webcast

Calithera will host a conference call and webcast on Monday June 6, 2016, at 6:30 p.m. CT to review the clinical data presented at ASCO (Free ASCO Whitepaper) from the ongoing Phase I study of CB-839. The live audio webcast can be accessed via the Investor section of the Company’s website at www.calithera.com. The conference call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international) and refer to conference ID 23768811. Please log in approximately 5-10 minutes before the event to ensure a timely connection. The archived webcast will remain available for 30 days following the call.

On June 6, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported the presentation of three posters featuring updated clinical data from its aldoxorubicin clinical trials at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3-7, 2016, at McCormick Place in Chicago (Press release, CytRx, JUN 6, 2016, View Source;p=RssLanding&cat=news&id=2175339 [SID:1234513038]).

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"The clinical data presented this year at ASCO (Free ASCO Whitepaper) continues to support the safety and activity of aldoxorubicin in multiple high unmet need tumor types, including in late-stage and heavily pre-treated patients," commented Daniel Levitt, M.D., Ph.D., CytRx’s Executive Vice President and Chief Medical Officer. "With over 550 cancer patients treated with aldoxorubicin to date, oncologists are becoming comfortable with the safety and utility profile of the drug."

The details for the ASCO (Free ASCO Whitepaper) 2016 poster presentations are as follows:

Title: Phase 2 study of aldoxorubicin in relapsed glioblastoma
Date/Time: June 4, 2016 1:00pm-5:00pm
Poster Session: Central Nervous System Tumors; Abstract 2027
Summary: This ongoing Phase 2 clinical trial is evaluating aldoxorubicin in patients with relapsed glioblastoma (GBM). Twenty-eight patients who had prior treatment with surgery, radiation and temozolomide therapy were enrolled and received either 250mg/m2 or 350mg/m2 of aldoxorubicin once every three weeks. To date, aldoxorubicin has demonstrated anti-tumor activity and appears to be relatively well-tolerated with patients receiving a median of 3 or 4 cycles (range 1-20) depending on the dose group. No evidence of central nervous system toxicity or clinically significant cardiac toxicity has been observed. Best responses in 21 subjects according to MRI were 3 patients with partial response (PR) and 7 patients with stable disease (SD). Additionally, two patients underwent surgery following aldoxorubicin treatment, and the pathology analysis of the removed tissue showed no viable tumor. The median overall survival was 8.6 months (95% CI: 7.8-10.1) with seven patients still on study and being followed.

This study provides the first evidence that aldoxorubicin’s albumin-binding mechanism allows it to cross the blood-brain barrier, unlike doxorubicin, and kill glioblastoma cells. Following the completion of this trial, CytRx will evaluate the clinical path forward for aldoxorubicin as a treatment for advanced GBM.

Title: Phase 1b study of aldoxorubicin + gemcitabine in metastatic solid tumors
Date/Time: June 5, 2016 8:00am-11:30am
Poster Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics; Abstract: 2523
Summary: This ongoing Phase 1b study is evaluating aldoxorubicin in combination with gemcitabine in patients with metastatic solid tumors. To date, 29 heavily pre-treated patients (median prior regimens 3-4; range 0-15) have been enrolled in four different dose combination cohorts. Of 18 evaluable patients, 13 of 18 (72%) had clinical benefit including two partial responses and 11 patients with stable disease. The confirmed partial responses were in a patient with ovarian cancer and a patient with uterine leiomyosarcoma. Across all dose groups the number of completed cycles range from 1-17, and cumulative doxorubicin exposure ranges from 208mg to 4,103mg. Doses of 200 mg/m2 aldoxorubicin with 500 mg/m2 gemcitabine appears to be best tolerated. Patients continue to be treated in the final dose cohort.

Although patients in this trial had a variety of different types of cancer, the future focus of this combination will be the treatment of ovarian and endometrial adenocarcinoma.

Title: Treatment of HIV-associated Kaposi’s sarcoma with aldoxorubicin
Date/Time: June 6, 2016 8:00am-11:30am
Poster Session: Sarcoma; Abstract: 11038
Summary: This ongoing open-label Phase 2 clinical trial is evaluating the efficacy and safety of low dose aldoxorubicin for the treatment of Kaposi’s sarcoma (KS) in HIV-infected patients. Fifteen patients have been enrolled and received either 50, 100, or 150 mg/m2 of aldoxorubicin once every three weeks. To date, significant anti-tumor activity has been observed. At these low doses, 11 of 13 (85%) patients have achieved partial responses at cycle 4, and at the end of the study, 8 of 12 (67%) patients have demonstrated partial responses. Two patients continue to be treated. Aldoxorubicin was very well-tolerated in these patients with advanced Kaposi’s sarcoma due to the low doses administered. Importantly, determining the drug concentration within the tumor, a key goal of the trial, was successfully achieved. In 12 of 14 (86%) patients for whom there was adequate tissue for analysis, higher doxorubicin concentrations were detected within the KS lesion relative to non-tumor tissue.

The high level of activity and important tolerability of low dose aldoxorubicin will allow long term usage in this very difficult to treat group of patients.

About Aldoxorubicin
The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.

On June 6, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) and Roivant Sciences Ltd. reported the formation of Myovant Sciences Ltd. ("Myovant"), a biopharmaceutical company focused on delivering innovative women’s health and prostate cancer solutions by efficiently advancing new medicines to market that have the potential to improve the lives of millions of patients (Press release, Takeda, JUN 6, 2016, View Source [SID:1234513109]). In addition, Lynn Seely, MD, an endocrinologist who led the development of XTANDI (enzalutamide) for the treatment of prostate cancer as the Chief Medical Officer of Medivation from 2005 to 2015, was named the President & Chief Executive Officer of Myovant Sciences, Inc.

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Myovant Partnership Summary
Takeda has granted Myovant an exclusive, worldwide license (excluding Japan and certain other Asian countries) to relugolix (TAK-385), a phase 3 drug candidate that has been evaluated in over 1,300 patients to date. Relugolix has successfully demonstrated significant clinical benefit and was generally well-tolerated across multiple, large, randomized phase 2 clinical trials in three different indications. Relugolix is being developed as an oral, once-daily, potential best-in-class gonadotropin-releasing hormone (GnRH) receptor antagonist for uterine fibroids, endometriosis and prostate cancer. Takeda will retain commercial rights for relugolix in Asian countries, including Japan, where Takeda is actively conducting two phase 3 registration studies for the treatment of uterine fibroids. Takeda has also granted Myovant an exclusive, worldwide license to RVT-602 (TAK-448), a novel, oligopeptide kisspeptin receptor agonist as a product candidate for the treatment of infertility in females. Financial terms of the partnership were not disclosed.

"With Takeda strengthening its focus around the core therapeutic areas of oncology, gastroenterology and central nervous system diseases, as well as establishing a strategy that embraces innovative partnerships, it is important that we seek alternatives to further develop and create value around promising assets that are either outside these areas of focus or where strategic partnership makes more sense for our business," said Andrew Plump, M.D., Ph.D., Chief Medical and Scientific Officer of Takeda. "The formation of Myovant Sciences represents such an innovative partnership arrangement to further advance relugolix by relying on Roivant’s and Myovant’s in-house development capabilities in the major markets where they are building deep expertise, while leveraging Takeda’s commercial presence in certain Asian territories."

"We are very pleased to partner with Takeda to meet the needs of patients suffering from hormone-driven diseases and disorders," said Vivek Ramaswamy, CEO of Roivant Sciences, Inc. "The creation of Myovant enables a ‘win-win’ outcome for both our partner and for patients by launching a company to address major unmet medical needs in women’s health, prostate cancer and beyond."

Appointment of Dr. Lynn Seely as President & Chief Executive Officer
Lynn Seely, MD, brings over 20 years of drug development and biopharmaceutical company leadership to her role as the President & Chief Executive Officer of Myovant Sciences, Inc. Most recently, Dr. Seely served as Chief Medical Officer of Medivation, Inc. from its early stages in March 2005 through October 2015. She served on the Executive Committee and led the development of XTANDI for the treatment of metastatic castration-resistant prostate cancer from IND-enabling studies through to NDA approval and post-approval clinical studies. Dr. Seely was responsible for building the clinical organization at Medivation, as well as the regulatory, quality, project management, medical affairs and biologics manufacturing functions. Dr. Seely currently serves on the board of directors of Blueprint Medicines Corporation, and she previously served as Vice President of Clinical Development at Anesiva, Inc. (formerly Corgentech) and at Cytyc Health Corporation. Dr. Seely received a medical degree from the University of Oklahoma College of Medicine and completed her residency in internal medicine at Yale-New Haven Hospital. After serving as Chief Resident in Internal Medicine at Yale University School of Medicine, she completed her basic science and clinical fellowship in endocrinology and metabolism at the University of California, San Diego.
"I look forward to delivering on Myovant’s mission to bring innovative new treatments to women suffering from diseases such as uterine fibroids and endometriosis and to men with prostate cancer," stated Dr. Lynn Seely, President & CEO of Myovant Sciences, Inc. "Relugolix and our partnership with Takeda represent an exceptional foundation on which to build this exciting new company."

About Relugolix
Relugolix is a once-daily, orally administered, potential best-in-class gonadotropin-releasing hormone (GnRH) receptor antagonist for the treatment of uterine fibroids and endometriosis, and a potential best- and first-in-class treatment for hormone-sensitive prostate cancer (HSPC). Relugolix has been evaluated in over 1,300 patients to date, and has successfully demonstrated significant clinical benefit and was generally well-tolerated across multiple, large, randomized phase 2 clinical trials in three different indications. Takeda is currently enrolling two phase 3 clinical trials of relugolix for registration in Japan for the treatment of uterine fibroids.

By inhibiting GnRH receptors in the pituitary gland, relugolix rapidly reduces circulating sex hormone levels leading to suppression of estrogen and testosterone. Suppression of these sex hormones improves the symptoms of women with uterine fibroids and endometriosis, and decreases prostate-specific antigen (PSA) levels in men with HSPC.

In a 216-patient phase 2 study for the treatment of uterine fibroids, women who received relugolix had a significant reduction in menorrhagia, or abnormally heavy bleeding during menstruation. In a 487-patient phase 2 study for the treatment of endometriosis, women who received relugolix had a significant reduction in both non-menstrual and menstrual pelvic pain. Based on these results, two phase 3 registration studies in women with uterine fibroids are underway in Japan (NCT02655237, NCT02655224). In two phase 2 studies in approximately 225 men with HSPC, which included control arms of either an injectable GnRH agonist (leuprolide acetate) or a GnRH antagonist (degarelix), respectively, oral once-daily relugolix suppressed serum testosterone to castrate levels and decreased PSA. The safety of relugolix across all phase 2 studies was generally well-tolerated, consistent with the mechanism of action.

The clinical experience to date, supported by an extensive preclinical development program, suggests that oral relugolix, administered once-daily, could be an important advancement in the treatment options available for women suffering from endometriosis and uterine fibroids. In addition, relugolix could provide men with HSPC an important new treatment option as the first oral GnRH receptor antagonist that offers an alternative to injectable therapies.

About RVT-602
RVT-602 (TAK-448) is a kisspeptin analog that acts to stimulate the physiologic release of GnRH and downstream hormones important in fertility such as luteinizing hormone. Recent evidence from trials performed in women undergoing In-vitro Fertilization (IVF) revealed that the native kisspeptin peptide has the potential to act as an alternative to human chorionic gonadotropin (hCG) or GnRH agonists in triggering egg maturation, an essential step in every IVF cycle.

About Myovant Sciences
Myovant Sciences is focused on innovative treatments for women’s health conditions and prostate cancer. The company’s lead program is relugolix, a phase 3 drug candidate for multiple indications, including uterine fibroids, endometriosis and prostate cancer. Myovant was formed through a strategic partnership between Roivant Sciences and Takeda. Additional information about Myovant Sciences is available through its website, www.myovant.com