On September 5, 2016 Innocrin Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing the oral, dual-mechanism, selective CYP17 lyase and androgen receptor (AR) inhibitor, seviteronel, for the treatment of breast and prostate cancers resistant to recently-approved hormonal therapies, reported the appointment of Edwina Baskin-Bey, MD as Chief Medical Officer, effective August 30, 2016 (Press release, Innocrin Pharmaceutical, OCT 5, 2016, View Source [SID:SID1234515611]).

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William Moore, PhD, Innocrin Chief Executive Officer stated, "I’m very pleased to welcome Edwina to the senior management team. Her strong development experience with AR pathway-targeted therapies such as abiraterone, enzalutamide, and apalutamide will serve Innocrin well as we move into later-stage Phase 2 breast and prostate cancer clinical studies."

Dr. Baskin-Bey has extensive oncology research and drug development experience. Immediately prior to joining Innocrin, she led several prostate cancer development programs at Janssen as Global Director of Oncology Development. Prior to Janssen, she was Global Director of Oncology Development at Astellas Pharma, with responsibility for the development of various (Phase 0-4) oncology products, including enzalutamide. Following receipt of a Doctorate in Medicine degree from Mount Sinai/NYU, Dr. Baskin–Bey trained as a general surgeon at the Mayo Clinic, performing basic scientific and clinical research through the National Institutes of Health.

Said Dr. Baskin-Bey, "I am excited to join Innocrin as the company expands its Phase 2 breast and castration-resistant prostate cancer development programs. Seviteronel holds great promise for late-stage breast and prostate cancer patients whose disease has progressed while on currently available therapies."

Innocrin also announced that once-daily oral seviteronel has advanced to Stage 2 in both the ER+ and AR+ triple-negative breast cancer (TNBC) groups in its ongoing open- label Phase 2 study (NCT02580448). Phase 2 oncology studies typically employ early ‘stopping rules’ that prevent large numbers of patients from being exposed to inactive drugs. Seviteronel has advanced to Stage 2 in both the ER+ and TNBC populations based upon early signs of significant therapeutic activity.

Dr. Baskin-Bey commented, "It is encouraging to see early signs of single-agent seviteronel clinical benefit in these two breast cancer patient populations which are in need of new treatment options. The combined inhibition of CYP17 lyase and the AR is a novel approach for the treatment of TNBC and ER+ disease. Seviteronel potentially addresses an unmet medical need for women whose breast cancer has progressed despite treatment with traditional ER-targeting agents or chemotherapy."

Innocrin will present updated Phase 2 clinical study results from 7:30-9:00 AM on December 8, 2016 at the San Antonio Breast Cancer Symposium (poster P2-08-04).

About Seviteronel (VT-464) Seviteronel is a once-daily oral therapeutic that can be given without prednisone. Seviteronel selectively inhibits CYP17 lyase, an enzyme needed for the synthesis of androgens and estrogens, and also directly blocks the AR.

It is thought that the AR may stimulate disease progression of breast cancer tumors that no longer are ER+ (e.g., are triple-negative) or are ER+ but have become resistant to ER-directed therapies such as aromatase inhibitors or tamoxifen. Preclinical study results, presented at the 2015 San Antonio Breast Cancer Symposium, confirmed that seviteronel blocks the growth of resistant ER+ and AR+ breast cancer cells more potently than enzalutamide.

A growing body of preclinical and clinical evidence shows that seviteronel blocks the growth of deadly, castration-resistant prostate cancer that is resistant to abiraterone (a CYP17 hydroxylase inhibitor) or enzalutamide (an AR antagonist). CRPC disease progression following treatment with abiraterone, enzalutamide or both represents a major unmet medical need due to the widespread and growing use of both agents, as well as the high cross-resistance between these agents (e.g., cancers that are resistant to abiraterone are typically resistant to enzalutamide and vice versa).

About Breast Cancer Each year over 230,000 women are diagnosed with breast cancer in the United States, with almost 40,000 deaths attributable to the disease. While estrogen deprivation is currently the standard of care for postmenopausal women with ER+ BCa, the majority of patients eventually develop resistance. ER+ patients comprise ~75% of all metastatic breast cancer cases, and TNBC accounts for ~15-20%. TNBC has a more aggressive course than ER+ BCa does but both have poor survival rates post-failure of endocrine and/or chemotherapy.

About Prostate Cancer Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in six will be diagnosed with prostate cancer in his lifetime. Prostate cancer afflicts nearly 240,000 men each year in the US and approximately 36,000 men die due to metastatic CRPC.

On October 5, 2016 Hercules Capital, Inc. (NYSE:HTGC) ("Hercules" or the "Company"), the leading specialty financing provider to innovative venture growth, pre-IPO and M&A stage companies backed by leading venture capital firms, reported its portfolio update for Q3 2016 (Press release, Hercules, OCT 5, 2016, View Source [SID:SID1234515612]).

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"Hercules Capital achieved another solid quarter of new originations and fundings as we continue to build our debt investment portfolio to our desired target of $1.35 billion," stated Manuel A. Henriquez, chairman and chief executive officer of Hercules. "While Q3 is normally our seasonally softest calendar quarter, our team continued to execute our ‘slow and steady’ growth and origination strategy achieving nearly $180 million of new commitments, including five new innovative venture growth stage technology and life sciences companies, backed by some of the leading venture capital firms in the U.S. The success of our origination team is a reflection of our strong brand and reputation within the venture capital and entrepreneurial communities."

Henriquez continued, "During the quarter, we also witnessed a healthy pick up in M&A activities with four companies announcing or completing M&A events, further bolstering our growing earnings spillover, as we look to harvest those capital gains for potential future distributions to our shareholders. We were also excited to see one of our portfolio companies, TPI Composites (NASDAQ:TPIC), successfully complete its IPO and become part of the Russell 2000 Index as it had nearly doubled its market capitalization prior to that event. During the quarter we were also able to bolster our liquidity and strengthen our balance sheet, positioning us well for the fourth quarter as we work to convert this strong liquidity into new interest-earning investments in a methodical fashion across our key investment markets driving additional growth in our debt investment portfolio."

New Debt and Equity Commitments for Q3 2016

As of September 30, 2016, Hercules has originated $178.0 million of debt and equity commitments to new and existing portfolio companies.

Five (5) new commitments to innovative venture growth stage companies:

Technology Portfolio – $45.0 Million

$25.0 million to a technology developer of enterprise analytics focused on customer and employee interactions and behaviors
$20.0 million to a software developer that designs a leading application for note taking, organizing and archiving
Life Sciences Portfolio – $85.0 Million

$35.0 million to a pharmaceuticals sales and distribution company
$30.0 million to a physician management and technology company that provides physician practice management and population health technology
$20.0 million to a biopharmaceutical company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology
New Commitments to Existing Portfolio Companies – $48.0 Million

Unscheduled Principal Repayments "Early Pay-Offs:"

As of September 30, 2016, Hercules received $84.2 million in unscheduled principal repayments "early pay-offs."

Portfolio Company IPO and M&A Activity in Q3 2016:

IPO Activities

1. TPI Composites, Inc., (NASDAQ:TPIC) the largest U.S.-based independent manufacturer of composite wind blades for the wind energy market, raised $69.0 million by offering 6.25 million shares of its common stock at $11.00 per share in July 2016. Hercules committed a total of $20.0 million in two (2) venture debt financings to TPI Composites beginning in June 2013. Hercules held warrants for 160 shares of Preferred Series B stock as of June 30, 2016, which represents an unrealized gain of approximately $1.2 million as of the closing price of $18.47 for TPI Composites on September 14, 2016.

2. As of September 30, 2016, Hercules held warrant and equity positions in four (4) portfolio companies that had filed Registration Statements in contemplation of a potential IPO, including:

Four companies filed confidentially under the JOBS Act
There can be no assurances that companies that have yet to complete their IPOs will do so.

M&A Activities

1. Celator Pharmaceuticals, Inc. (NASDAQ:CPXX), a pharmaceutical company developing new and more effective therapies to treat cancer, was acquired by Jazz Pharmaceuticals, Inc. (NASDAQ:JAZZ), an international biopharmaceutical company focused on improving patients’ lives by identifying, developing and commercializing meaningful products that address unmet medical needs, for $30.25 per share. The transaction closed on July 12, 2016. Hercules initially committed $15.0 million in venture debt financing to Celator Pharmaceuticals in May 2014. The Company recognized a net realized gain of approximately $1.5 million from the sale of shares, generating a fully realized internal rate of return ("IRR") of approximately 19.8% from its loan repayments and equity/warrant gains.

2. ReachLocal, Inc. (NASDAQ:RLOC), a leader in powering online marketing, helping local businesses grow and operate their business better with leading technology and expert service, was acquired by Gannett Co., Inc., (NYSE:GCI), a next-generation media company committed to strengthening communities across the company’s network, for $4.60 per share in cash, via a tender offer. The transaction closed on August 9, 2016. Hercules initially committed $25.0 million in venture debt financing to ReachLocal in April 2015. The Company recognized a net realized gain of $610,000 from the transaction, generating a fully realized IRR of approximately 24.1% from its loan repayments and equity/warrant gains.

3. TouchCommerce, a technology partner and leader in digital customer service and engagement solutions, was acquired by Nuance Communications, Inc. (NASDAQ:NUAN), a leading provider of voice and language solutions for businesses and consumers around the world, for $215.0 million in total consideration. The transaction closed on August 16, 2016. Hercules committed a total of $18.0 million in three (3) venture debt financings to TouchCommerce beginning in June 2013. Hercules held warrants for 2.3 million shares of Preferred Series E stock, as of June 30, 2016, which represents a realized gain of approximately $698,000 and an unrealized gain of approximately $770,000 as of the closing price of $14.46 for Nuance Communications on September 14, 2016.

4. IronPlanet, a leading online marketplace for used heavy equipment and other durable assets, announced that it had entered into a definitive agreement on August 29, 2016 under which Ritchie Bros. Auctioneers Incorporated (NYSE & TSX: RBA), the world’s largest industrial auctioneer and a leading equipment distributor, will acquire IronPlanet for approximately US $758.5 million, subject to customary closing adjustments. Hercules initially committed $37.5 million in venture debt financing to IronPlanet in October 2014. Hercules currently holds warrants for 1.2 million shares of Preferred Series D stock, as of June 30, 2016.

On October 4, 2016 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported that it will present preclinical data and preliminary biomarker data from its ongoing Phase 1/1b study of CPI-444 as a single agent, and in combination with Genentech’s TECENTRIQ (atezolizumab), in poster presentation sessions at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress, which is taking place October 7-11 at the Bella Center in Copenhagen, Denmark (Press release, Corvus Pharmaceuticals, OCT 4, 2016, View Source;p=RssLanding&cat=news&id=2209051 [SID:SID1234515572]).

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The ESMO (Free ESMO Whitepaper) abstracts are now available at www.esmo.org. Following are details for each poster presentation.

SUNDAY, OCTOBER 9
ABSTRACT #: 1068P
ABSTRACT TITLE: Adenosine A2A receptor antagonist, CPI-444, blocks adenosine-mediated T cell suppression and exhibits anti-tumor activity alone and in combination with anti-PD-1 and anti-PD-L1
POSTER PRESENTER: Stephen Willingham, Ph.D., Senior Scientist, Corvus
POSTER PRESENTATION TIME: 13:00-14:00 CEST
POSTER DISPLAY LOCATION: Hall E

ABSTRACT #: 1105TIP
ABSTRACT TITLE: Phase 1/1b multicenter trial of the adenosine A2a receptor antagonist (A2aR) CPI-444 as single agent and in combination with atezolizumab (ATZ) in patients (Pts) with advanced cancers
POSTER PRESENTER: Ginna G. Laport, M.D., Vice President, Clinical Development, Corvus
POSTER PRESENTATION TIME: 13:00-14:00 CEST
POSTER DISPLAY LOCATION: Hall E

MONDAY, OCTOBER 10
ABSTRACT #: 389P
ABSTRACT TITLE: Biomarker and clinical activity of CPI-444, a novel small molecule inhibitor of A2A receptor (A2AR), in a Phase 1b study in advanced cancers
POSTER PRESENTER: Ian McCaffery, Ph.D., Vice President, Translational Sciences, Corvus
POSTER PRESENTATION TIME: 13:00-14:00 CEST
POSTER DISPLAY LOCATION: Hall E

On October 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has received a second Breakthrough Therapy Designation (BTD) from the United States Food and Drug Administration (FDA) for its ALK inhibitor, Alecensa (alectinib) (Press release, Hoffmann-La Roche , OCT 4, 2016, View Source [SID:SID1234515583]). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.

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"The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "The decision by the FDA to grant a second breakthrough therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor."

This second breakthrough therapy designation is based on the results of the open-label, randomised phase III J-ALEX study, which were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. J-ALEX compared the efficacy and safety of Alecensa with crizotinib in 207 Japanese people with ALK-positive, advanced or recurrent NSCLC who either had not been treated with chemotherapy or had received one prior line of chemotherapy. Results from the study demonstrated that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66% compared to crizotinib, whilst maintaining a favourable tolerability and safety profile consistent with that observed in previous studies.

The FDA’s Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible. Alecensa received its first FDA BTD in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.

Alecensa is currently available in the US and Israel to ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib, and in Japan to ALK-positive unresectable, recurrent or advanced NSCLC patients. In addition, an ongoing global, randomised phase III trial called ALEX is comparing Alecensa to Xalkori as an initial (first-line) treatment for people with advanced ALK-positive NSCLC.

About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomised Phase III study that compared the efficacy and safety of Alecensa to crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK inhibitor. People were randomised to the Alecensa group or the crizotinib group in a one-to-one ratio. Results include:

Alecensa reduced the risk of disease worsening or death (PFS) by 66 percent compared to crizotinib (HR=0.34, 99 percent CI: 0.17-0.70, p<0.0001).

Median PFS was not reached in the Alecensa arm (95 percent CI: 20.3 months-not estimated) versus 10.2 months in the crizotinib arm (95 percent CI: 8.2-12.0).

Grade 3-4 adverse events (AE) occurred with lesser frequency in the Alecensa arm compared to the crizotinib arm (27 percent vs. 51 percent).

The most common AE occurring with > 30 percent frequency with Alecensa was constipation (36 percent). The most common AEs for crizotinib were nausea (74 percent), diarrhoea (73 percent), vomiting (59 percent), visual disturbance (55 percent), alteration in taste (dysgeusia, 52 percent), constipation (46 percent), and an elevation in liver enzymes called alanine transaminase (ALT, 32 percent) and aspartate transaminase (AST, 31 percent).

About Alecensa
Alecensa (RG7853/AF-802/CH5424802) is an oral medicine created at Chugai Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In two key phase II studies, NP28761 and NP28673, Alecensa shrank tumours in up to 44% of people with ALK-positive NSCLC who progressed on crizotinib. Alecensa also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain
Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord.

One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise
Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III studies of Alecensa include a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

About ALK-positive non-small cell lung cancer
Lung cancer is the biggest cancer killer, causing 1.59 million deaths globally each year. NSCLC is the most common type of lung cancer, and is the leading cause of cancer-related deaths in Europe and across the world, accounting for approximately 85% of lung cancer cases. ALK-positive NSCLC occurs in approximately 5% of patients with advanced NSCLC, translating to about 75,000 patients being diagnosed with the disease annually. It is almost always found in people with a specific type of NSCLC called adenocarcinoma, and is more common in light or non-smokers.

On October 4, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that its board of directors has approved a plan for a reverse split of the Company’s common stock to increase its share price and reduce the number of authorized and outstanding shares (Press release, Cascadian Therapeutics, OCT 4, 2016, View Source [SID:SID1234515581]).

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"The board and management have worked diligently on several facets of the Company this year to position it for the future, including bringing in new management, and solidifying our product development and regulatory strategies. With this action, we are helping ensure that the necessary financial structure is in place to execute our plans," said Scott Myers, President and CEO of Cascadian Therapeutics. "We believe this proposed change will make our stock accessible to a wider range of institutional investors, benefiting all stockholders."

Cascadian is advancing tucatinib (ONT-380), its lead product candidate in Phase 2 development for HER2+ metastatic breast cancer patients, with and without brain metastases. The Company plans to report updated clinical data from its Phase 1b tucatinib combination study with capecitabine and trastuzumab at the San Antonio Breast Cancer Symposium in December. It also expects to provide an update during the fourth quarter on its regulatory strategy for tucatinib.

Cascadian plans to hold a special meeting on November 18, 2016 at the Company’s headquarters to obtain stockholder approval of the reverse split, proposed at a ratio of not less than 1-for-4 and not greater than 1-for-10, and to reduce the total authorized shares of the Company’s common stock by a ratio of two times (2x) the reverse split ratio. The Company believes these proposals will provide shares to operate and fund the Company’s programs. The Cascadian board of directors will set the exact range and timing of the reverse split and share reduction of authorized common stock at its discretion following approval by stockholders and before December 31, 2016. The Company filed a preliminary proxy statement regarding the special meeting with the U.S. Securities and Exchange Commission. The preliminary proxy statement and the Company’s 2015 annual report can be accessed for free at www.sec.gov. The Company’s 2015 annual report can also be accessed for free on SEDAR in Canada. Investors are encouraged to read the preliminary proxy statement because it includes important information regarding the special meeting.

Our board of directors is soliciting proxies in connection with this special meeting. Directors and executive officers of Cascadian have no substantial interests, directly or indirectly, in the matters to be voted upon at the special meeting, except to the extent of their ownership of shares of Cascadian’s common stock and securities convertible to or exercisable for common stock.