On March 3, 2016 GTx, Inc. (Nasdaq: GTXI) reported financial results for the fourth quarter and year ended December 31, 2015, and highlighted recent accomplishments and upcoming milestones (Press release, GTx, MAR 3, 2016, View Source;p=RssLanding&cat=news&id=2145524 [SID:1234509359]). The Company is currently enrolling patients in three clinical trials: two trials evaluating enobosarm as a potential treatment for women with advanced breast cancer, and another assessing enobosarm as a potential treatment for stress urinary incontinence in postmenopausal women.

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"In 2015, we continued to make important progress across our pipeline assets, and while our primary focus continues to be the development of enobosarm to potentially treat advanced breast cancer and our SARD technology, we have diversified our therapeutic opportunities to include SARMs for stress urinary incontinence and Duchenne muscular dystrophy," said Dr. Robert J. Wills, Executive Chairman of GTx.

Corporate Highlights and Anticipated Milestones

Enobosarm in Breast Cancer: The Company’s lead product candidate, a selective androgen receptor modulator (SARM), is being developed as a targeted treatment for two advanced breast cancer indications: (i) estrogen receptor positive (ER+) and androgen receptor positive (AR+) breast cancer, and (ii) AR+ triple negative breast cancer (TNBC). For both clinical trials, the primary efficacy endpoint will be clinical benefit, which is defined as a complete response, partial response or stable disease.

ER+/AR+ breast cancer: currently expect to enroll the first stage of the open-label, Phase 2 clinical trial of enobosarm in women with metastatic or locally advanced, ER+/AR+ breast cancer by mid-year in order to report preliminary results by the end of 2016. While the first stage of the trial will evaluate 18 patients for each of the two dosing arms, 9 mg and 18 mg of enobosarm, the trial is designed to enroll up to 118 patients to obtain data from 44 evaluable patients in each study arm (a total of 88 evaluable patients) to assess the primary efficacy objective of clinical benefit response following 24 weeks of treatment.

AR+ TNBC: currently expect to enroll the first stage of the open-label, proof-of-concept Phase 2 clinical trial of 18 mg of enobosarm in women with advanced AR+ TNBC by mid-year in order to report preliminary results by the end of 2016. While the first stage will include 21 evaluable patients, the trial is designed to enroll up to 55 patients in total in order to obtain data from 41 evaluable patients to assess the primary efficacy objective of clinical benefit response following 16 weeks of treatment.

SARMs in Non-Oncologic Indications: The Company is exploring SARMs as potential treatments for both stress urinary incontinence (SUI) and Duchenne muscular dystrophy (DMD), a rare disease characterized by progressive muscle degeneration and weakness.

SUI: enrolled first patient in a Phase 2 proof-of-concept clinical trial of 3 mg of enobosarm to treat up to 35 postmenopausal women with SUI, the first clinical trial to evaluate a SARM for SUI. Top-line data from the Phase 2 clinical trial is anticipated by the end of 2016.

DMD: the Company’s preclinical studies have continued to confirm beneficial effects from SARMs in mice genetically altered to simulate DMD, compared to control groups.

DMD mice were treated with one of three different SARM compounds, including enobosarm, and each SARM cohort demonstrated increases in body weight, muscle mass, muscle performance (grip strength) and cardiac function, compared to control groups;
Histologically, in SARM-treated mice, skeletal muscles demonstrated a reduction in necrosis, fibrosis, and centrally nucleated cells, which are accepted markers of skeletal muscle atrophy; and

A SARM also markedly reduced the fibrosis of cardiac muscle, which is relevant since most DMD patients will develop cardiomyopathy as the disease progresses.

SARDs in Prostate Cancer: Selective Androgen Receptor Degrader (SARD) technology is being evaluated as a potentially novel treatment for men with castration-resistant prostate cancer (CRPC), including those who do not respond or are resistant to currently approved therapies. The Company believes that its SARD compounds will degrade multiple forms of the androgen receptor, including AR splice variants, such as AR-V7.

CRPC: lead SARD compounds are currently being evaluated in additional preclinical studies to select the best SARD compounds for continued development, as well as to develop data necessary to initiate first in human clinical trials in 2017.

Fourth Quarter and Year-End 2015 Financial Results

As of December 31, 2015, cash and short-term investments were $29.3 million compared to $49.3 million at December 31, 2014.
Research and development expenses for the quarter ended December 31, 2015 were $3.9 million compared to $3.3 million for the same period of 2014. Research and development expenses for the year ended December 31, 2015 were $13.6 million compared to $20.9 million for the year ended December 31, 2014.

General and administrative expenses for the quarter ended December 31, 2015 were $2.1 million compared to $2.2 million for the same period of 2014. General and administrative expenses for the year ended December 31, 2015 were $8.2 million compared to $9.5 million for the year ended December 31, 2014.

The net loss for the quarter ended December 31, 2015 was $3.2 million compared to a net loss of $14.5 million for the same period in 2014. The net loss for the quarters ended December 31, 2015 and December 31, 2014 included a non-cash gain of $2.7 million and a non-cash loss of $8.8 million, respectively, related to the change in the fair value of the Company’s warrant liability. The net loss for the year ended December 31, 2015 was $18.7 million compared to a net loss of $39.4 million for the year ended December 31, 2014. The net loss for the years ended December 31, 2015 and December 31, 2014 included a non-cash gain of $3.1 million and a non-cash loss of $8.8 million, respectively, related to the change in the fair value of the Company’s warrant liability.

GTx had approximately 140.4 million shares of common stock outstanding as of December 31, 2015. Additionally, there remain warrants outstanding to purchase approximately 64.3 million shares of GTx common stock at an exercise price of $0.85 per share.

On March 3, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported financial results for the year ended December 31, 2015, and also provided an overview of certain corporate developments (Press release, Verastem, MAR 3, 2016, View Source;p=RssLanding&cat=news&id=2145548 [SID:1234509354]).

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"We are developing treatments that reduce cancer stem cells and modulate the local tumor microenvironment to allow both cancer treatments and the immune system to do their job more efficiently," said Robert Forrester, President and Chief Executive Officer of Verastem. "Our recently announced collaborations with Pfizer and Merck KGaA, and with Merck & Co. and Washington University in St. Louis, to evaluate the combination of our FAK inhibitors with immune-oncology agents speak to the understanding among the clinical community that innovative combination therapies have the potential to complement and enhance existing therapies. We begin 2016 with a strong balance sheet and expect significant progress from our ongoing programs targeting high unmet need cancers including non-small cell lung, ovarian, lymphoma, mesothelioma and pancreatic cancer. We are also planning for several trial initiations this year and we look forward to keeping you updated on our progress."

Recent Highlights:

Focal Adhesion Kinase Inhibition Program
There is a growing body of preclinical research suggesting that focal adhesion kinase (FAK) inhibition, when combined with PD-1 inhibitors, may increase the anti-tumor activity of immunotherapeutic agents such as programmed death receptor 1 (PD-1) and its corresponding ligand (PD-L1). Research reports on this were published in the September 24, 2015 edition of Cell and presented at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), the 2015 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference, and the 2016 Immunotherapy World Conference.

The data presented provide an overview of preclinical research to date demonstrating how FAK inhibition increases the influx of cytotoxic T cells into tumors while reducing immuno-suppressive and stromal density barriers to antitumor immune attack. This research suggests that FAK inhibition creates a more favorable tumor microenvironment for the antitumor effects of immune checkpoint inhibitors and potentially other immunotherapies. Verastem expects multiple combination clinical trials, building on previously reported signals of clinical activity in addition to preclinical rationale, to be conducted this year in ovarian cancer, pancreatic cancer, mesothelioma and non-small cell lung cancer. To date, the following clinical studies have been announced:

Clinical Collaboration with Pfizer and Merck KGaA to Evaluate Combination of VS-6063 and Avelumab in Ovarian Cancer – In March 2016, the companies announced their entry into a clinical trial collaboration agreement to evaluate the investigational combination of Verastem’s focal adhesion kinase (FAK) inhibitor VS-6063 and Pfizer/Merck KGaA’s anti-PD-L1 immunotherapy avelumab.

Verastem has previously reported initial signs of clinical activity in patients with ovarian cancer when VS-6063 is used in combination with paclitaxel. Under the terms of the agreement, the parties will conduct a planned Phase 1/1b clinical trial evaluating escalating doses of the combination of VS-6063 and avelumab as a potential treatment option for patients with advanced ovarian cancer.

Washington University in St. Louis Initiated a Clinical Study of VS-6063 in Combination with Merck & Co.’s Pembrolizumab and Gemcitabine in Pancreatic Cancer – In January 2016, Verastem announced the initiation of a Phase 1 dose-escalation study at Washington University to evaluate Verastem’s FAK inhibitor VS-6063 in combination with Merck & Co.’s anti-PD-1 immunotherapy pembrolizumab and gemcitabine in patients with pancreatic cancer.

In addition, Verastem’s second FAK inhibitor, VS-4718, has demonstrated a generally well-tolerated safety profile in a single-agent ascending dose study and is suitable for progression into further clinical studies. Confirmatory cohorts to determine the recommended Phase 2 dose as well as expansion cohorts in biopsiable disease are planned for 2016. Additional studies for VS-4718 in 2016 include:

Combination Trial of VS-4718 and Gemcitabine/Abraxane – A clinical trial of VS-4718 in combination with gemcitabine and Abraxane was recently initiated. Initial results of the dose escalation study are expected by year end 2016. Following results from the dose escalation, an expansion cohort of VS-4718 + Gemcitabine/Abraxane vs Gemcitabine/Abraxane alone in patients with pancreatic cancer is planned.

Dual PI3K/mTORC1/2 Inhibition Program
The maximum tolerated dose of VS-5584 has been reached in the Phase 1, single-agent study of VS-5584, and the recommended Phase 2 dose is being confirmed. Reductions in pharmacodynamic markers of PI3K and mTOR activity and clinical activity has been observed in some tumor types. Additional studies for VS-5584 in 2016 include:

Confirmatory Recommended Phase 2 Dose and Expansion Cohorts – A cohort of the single-agent VS-5584 trial is enrolling additional patients with solid tumors or lymphomas to confirm the recommended dose for Phase 2 trials. Expansion cohorts in ovarian and endometrial cancer, non-hodgkins lymphoma, and chronic lymphocytic leukemia are planned for 2016.

Full Year 2015 Financial Results
As of December 31, 2015, Verastem had cash, cash equivalents and investments of $110.3 million compared to $92.7 million as of December 31, 2014. Verastem used $45.6 million for operating activities during the year ended December 31, 2015 ("2015 Period").

Net loss for the 2015 Period was $57.9 million, or $1.61 per share, as compared to a net loss of $53.4 million, or $2.07 per share, for the year ended December 31, 2014 ("2014 Period"). Net loss for the 2015 Period and 2014 Period includes non-cash stock-based compensation expense of $9.7 million and $12.1 million, respectively.

Research and development expense for the 2015 Period was $40.6 million compared to $35.4 million for the 2014 Period. The $5.2 million increase from the 2014 Period to the 2015 Period was primarily related to an increase of $5.8 million in contract research organization expense for outsourced biology, chemistry, development and clinical services, which includes our clinical trial costs, an increase in personnel related costs of $1.4 million, and an increase of approximately $558,000 in consulting expense. These increases were partially offset by decreases of $1.3 million in stock-based compensation expense and $1.2 million in license fees.

General and administrative expense for the 2015 Period was $17.6 million compared to $18.2 million for the 2014 Period. The decrease of approximately $525,000 from the 2014 Period to the 2015 Period primarily resulted from decreases in stock-based compensation expense of $1.1 million and approximately $446,000 in professional fees. These decreases were offset by an increase of approximately $856,000 in personnel costs.

The number of outstanding common shares as of December 31, 2015, was 36,941,261.

Financial Guidance
Based on current operating plans, we expect to have sufficient cash, cash equivalents and short-term investments to fund our research and development programs and operations into 2018.

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. VS-6063 (defactinib) and VS-4718 are orally available compounds that are potent inhibitors of FAK. VS-6063 and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. VS-6063 and VS-4718 are currently being studied in multiple clinical trials for their ability to improve patient survival.

About VS-5584
VS-5584 is an orally available compound that has demonstrated potent and highly selective activity against class 1 PI3K enzymes and dual inhibitory actions against mTORC1 and mTORC2. In preclinical studies, VS-5584 has been shown to reduce the percentage of cancer stem cells and induce tumor regression in chemotherapy-resistant models. Verastem is currently conducting a dose escalation trial of VS-5584 in patients with advanced solid tumors.