1stOncology™: Cancer Intelligence Service – Page 15750 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Aegerion Pharmaceuticals and QLT Inc. Agree to Strategic Merger

On June 15, 2016 Aegerion Pharmaceuticals, Inc. (NASDAQ:AEGR) ("Aegerion") and QLT Inc. (NASDAQ:QLTI) (TSX:QLT) ("QLT") reported that they have entered into a definitive merger agreement under which Aegerion will be merged with a wholly owned indirect subsidiary of QLT (Press release, QLT, JUN 15, 2016, View Source;p=RssLanding&cat=news&id=2177689 [SID:1234513357]). Upon completion of the proposed merger, each outstanding share of Aegerion common stock will be exchanged for 1.0256 shares of QLT common stock. QLT plans to change its name upon the closing of the proposed transaction to Novelion Therapeutics Inc. ("Novelion") and its common shares will trade on the NASDAQ Global Select Market and the Toronto Stock Exchange.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

A broad-based investor syndicate comprised of both new investors and existing shareholders of both companies (collectively, the "Investors") has committed to invest approximately $22 million in QLT and to vote in favor of the proposed transaction. This investment would be funded immediately prior to the transaction close and is expected to provide Novelion with additional capital to support future operations and the potential opportunity for targeted business development initiatives. Assuming completion of the proposed merger by the end of the third quarter of 2016, Novelion is expected to have an unrestricted cash balance of over $100 million.

The proposed transaction, which has been approved by the Boards of Directors of both companies, is expected to close late in the third quarter or during the fourth quarter of 2016, subject to approval by shareholders representing a majority of the outstanding common stock of each of QLT and Aegerion as well as other closing conditions.

Strategic Merger Designed to Transform Both Companies and Create Significant Value for Shareholders

The proposed merger is expected to create a strong, rare disease-focused global biopharmaceutical company with a diversified portfolio consisting of Aegerion’s two commercially branded products, Juxtapid (lomitapide) capsules and Myalept (metreleptin), and QLT’s QLT091001 ("Zuretinol Acetate" or "Zuretinol"), a Phase 3-ready Ultra-Orphan Fast Track and Orphan Drug designated asset being developed for the treatment of Inherited Retinal Disease caused by underlying mutations in RPE65 or LRAT genes ("IRD"), which indication comprises Leber Congenital Amaurosis ("LCA") and Retinitis Pigmentosa ("RP").

Aegerion’s Chief Executive Officer, Mary Szela, who will serve as Chief Executive Officer of Novelion following the close of the transaction, said: "We believe QLT’s clinical development team, and meaningful cash position, and Aegerion’s commercialization expertise will help unlock significant value in QLT’s Zuretinol asset and enable Novelion to pursue important milestones across a commercial and late-stage portfolio, including potential regulatory approval in Japan for Juxtapid and potential regulatory filings in Europe for Myalept. I believe that this proposed merger represents a fresh start and an opportunity to create significant value, and I look forward to driving our programs forward."

Dr. Geoffrey F. Cox, Ph.D., QLT’s Interim Chief Executive Officer, said: "Given the resource requirements for QLT to build out a global commercial infrastructure designed to most effectively maximize the value of our promising ultra-orphan Zuretinol asset, the QLT board determined that it would be advantageous to join forces with a strategic partner possessing the relevant orphan product infrastructure. We believe Aegerion and QLT are ideal complements, and we are confident that this transaction achieves virtually all of the principal goals and objectives of our strategic review process. In addition, QLT is expected to benefit from greater scale and diversification, as well as from a more liquid stock."

QLT’s Promising Ultra-Orphan Pipeline Product (Zuretinol acetate)

QLT is developing a synthetic retinoid product candidate (Zuretinol acetate) for the potential treatment of Inherited Retinal Disease caused by underlying mutations in RPE65 or LRAT genes (IRD) that prevent adequate functioning of the retinoid cycle, which indication comprises LCA and RP. LCA and RP are two forms of severe IRD resulting in progressive vision loss starting in childhood and leading to inevitable blindness.

There are currently no U.S. Food and Drug Administration ("FDA") or European Medicines Agency ("EMA") approved pharmacologic treatments for either LCA or RP, underscoring the significant unmet medical need. Zuretinol acetate is expected to advance to Phase 3 clinical trials in the third quarter of 2016 and has Orphan Drug designation from both FDA and EMA, as well as FDA Fast Track designation. As an oral product, Zuretinol acetate is being studied for its potential to treat the retinas of both eyes simultaneously. If approved, QLT believes it is possible to achieve first-line positioning in the treatment of IRD.

Private Placement

In combination with the proposed merger transaction, a broad-based investor syndicate will subscribe to purchase approximately $22 million in shares of QLT common stock for a purchase price of $1.76 per share is subject to the satisfaction or waiver of the conditions to closing the merger. These commitments would be funded immediately prior to merger closing to provide Novelion additional capital to support future operations and the potential opportunity for targeted business development initiatives.

The investor syndicate includes new investors, including Deerfield, and a broad group of existing Aegerion and QLT shareholders, including Armistice Capital, Broadfin Capital, Healthcare Value Capital, JW Asset Management, K2 & Associates Investment Management, Sarissa Capital, Tiger Legatus Capital Management, and others.

The subscription by the Investors to purchase shares of QLT common stock is subject to the satisfaction or waiver of the conditions to closing the merger. Each of the Investors has also agreed to vote its shares in QLT and Aegerion in favor of the transaction.

Corporate Governance

Following the close of the transaction, Novelion is expected to have its principal headquarters in Vancouver, British Columbia, where QLT is currently located, with business operations in Cambridge, Massachusetts.

The Board of Directors of Novelion will be comprised of ten members, including four QLT designees, four Aegerion designees and two shareholder representatives, one from Broadfin Capital and the other from Sarissa Capital. For a period of time that expires shortly after Novelion’s 2017 annual shareholder meeting, Sarissa Capital also has the right to designate an additional director to the Novelion Board.

Transaction Details

Under the terms of the merger agreement, Aegerion will become a wholly-owned indirect subsidiary of QLT, and each existing share of Aegerion common stock will be converted into the right to receive 1.0256 common shares of Novelion. As a result of the structure of this transaction, a repayment obligation with respect to Aegerion’s outstanding convertible notes will not be triggered.

The exchange ratio for the transaction is subject to certain adjustments if Aegerion’s previously disclosed securities class action litigation and Department of Justice ("DOJ") and Securities and Exchange Commission ("SEC") investigations are resolved prior to closing for amounts in excess of negotiated thresholds. In the event the class action litigation or DOJ and SEC investigations are not settled prior to closing, and in order to mitigate the risk of certain losses from these outstanding matters after transaction close, QLT will enter into a warrant agreement pursuant to which warrants will be issued to QLT shareholders and the Investors that would be exercisable for additional Novelion shares if the class action litigation or DOJ and SEC investigations are subsequently resolved for amounts in excess of negotiated thresholds.

Following completion of the proposed merger, QLT shareholders, including the Investors, who are investing in QLT immediately prior to closing, are expected to own approximately 67% and current Aegerion shareholders will own approximately 33% of Novelion’s common shares.

Concurrent with signing, Aegerion and QLT have entered into a loan agreement under which QLT has agreed to loan Aegerion up to $15 million for working capital. Aegerion will borrow $3 million in connection with execution of the Merger Agreement and may borrow up to $3 million per month in subsequent months, subject to certain conditions, if and to the extent such amounts are necessary in order for Aegerion to maintain an unrestricted cash balance of $25 million.

In addition to shareholder approval, the merger is subject to stock exchange approvals and other closing conditions, including, among others, regulatory approval and completion of a specified minimum of the private placement in QLT by the Investors.

Greenhill & Co., LLC is acting as the exclusive financial advisor to QLT and Weil, Gotshal & Manges LLP is serving as QLT’s legal counsel. J.P. Morgan is acting as the exclusive financial advisor to Aegerion and Ropes & Gray LLP is serving as Aegerion’s legal counsel.

Delcath Announces Acceptance Of Abstract For Presentation At 6th European Post-Chicago Melanoma/Skin Cancer Meeting

On June 15, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on oncology with an emphasis on the treatment of primary and metastatic liver cancers, reported that data from a large single hospital experience conducted at Southampton University Hospital in the United Kingdom has been accepted for oral presentation at the 6th European Post-Chicago Melanoma/Skin Cancer Meeting to be held in Munich, Germany at the Leonardo Royal Hotel from June 30 – July 1, 2016 (Press release, Delcath Systems, JUN 15, 2016, View Source;p=RssLanding&cat=news&id=2177653 [SID:1234513355]).

The abstract authored by I. Karydis, et al. is titled, "Chemosaturation via percutaneous hepatic perfusion – an update on a single centre experience of treating metastatic uveal melanoma." Additional information about the Post-Chicago scientific program can be found here and the complete abstract will be available for download approximately 10 days prior to the congress.

Rgenix Announces $33 Million Series B Financing to Develop First-in-Class Cancer Therapeutics

On June 15, 2016 Rgenix, a cancer therapeutics company developing first-in-class drugs targeting novel cancer pathways, reported a $33 million Series B financing led by Novo A/S and Sofinnova Partners, with participation from existing investors including Partnership Fund for New York City, Alexandria Venture Investments, and Conegliano Ventures LP (Press release, Rgenix, JUN 15, 2016, View Source [SID1234523088]). The financing will support clinical development of Rgenix’s lead drug candidates, RGX-104 and RGX-202, as well as further development of its therapeutics pipeline.

"We are thrilled to have attracted top-tier investors to advance development of our novel cancer therapeutics"

Tweet this
"We are thrilled to have attracted top-tier investors to advance development of our novel cancer therapeutics," said Masoud Tavazoie, M.D. Ph.D., Chief Executive Officer and co-founder of Rgenix. "This financing validates the potential of our lead immunotherapy RGX-104, which will be entering clinical trials this fall, and also demonstrates the strength of our discovery platform, developed in the laboratory of Rgenix co-founder Dr. Sohail Tavazoie at The Rockefeller University. The funding will enable our team to deliver an innovative therapy to cancer patients while simultaneously pushing forward our pipeline of other novel drug candidates."

Antoine Papiernik, Managing Partner at Sofinnova Partners, commented: "We are very excited to back such a high quality team at Rgenix. We also believe that RGX-104 could revolutionize treatment to cancer patients that today lack effective therapies."

Despite recent advances in cancer therapy, most patients will eventually succumb to their disease due to drug resistance and immune evasion. RGX-104 is a small molecule that reverses immune evasion and drug resistance by targeting immunosuppressive cells in the tumor microenvironment via a novel pathway, resulting in strong anti-tumor activity in several drug-resistant cancer types in pre-clinical models, both as a single agent and in combination with approved immunotherapies such as PD-1 inhibitors. The target of RGX-104 was discovered using Rgenix’s miRNA platform that has yielded several new cancer targets across multiple prevalent cancer types.

"We are excited to support Rgenix’s novel approach to treating cancers of high unmet need," said Nilesh Kumar, Senior Principal of Novo Ventures*. "Rgenix has an exciting platform founded on strong science from The Rockefeller University; the lead program is a first in class opportunity addressing a key mechanism in tumor immunosuppression in various cancer types."

In connection with the financing, Nilesh Kumar of Novo Ventures and Antoine Papiernik of Sofinnova Partners will join the Rgenix Board of Directors together with existing members, including Executive Chairman Eric Rowinsky, M.D., Masoud Tavazoie, M.D. Ph.D., Nancy Chang, Ph.D., and Saeed Tavazoie, Ph.D.

Roche's Gazyvaro approved in Europe in combination with bendamustine for people with previously treated follicular lymphoma

On June 16, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Commission has approved Gazyvaro (obinutuzumab) in combination with bendamustine chemotherapy followed by Gazyvaro maintenance in people with follicular lymphoma who did not respond or who progressed during or up to six months after treatment with MabThera (rituximab) or a MabThera-containing regimen (Press release, Hoffmann-La Roche , JUN 15, 2016, View Source [SID:1234513393]).

The approval is based on results from the pivotal phase III GADOLIN study which showed that Gazyva/Gazyvaro plus bendamustine, followed by Gazyva/Gazyvaro alone resulted in a 52 percent reduction (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001) in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone, as evaluated by an independent review committee (IRC). As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001). People who received the Gazyva/Gazyvaro regimen also showed a 38 percent reduction (HR=0.62, 95 percent CI 0.39-0.98) in the risk of death (OS) compared to those who received bendamustine alone.

"Today’s approval is a significant milestone in the treatment of people with follicular lymphoma in Europe," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "For those who fail to achieve durable disease control with MabThera-based treatment, Gazyvaro plus bendamustine is an important new treatment option that has been shown to reduce the risk of disease progression or death by more than half."

Every day, more than 50 people in Europe are diagnosed with follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin lymphoma (NHL).1,2 During initial therapy, response rates to MabThera-based treatment, the current standard of care, are greater than 90 percent, but there is no cure and people will eventually relapse.3,4 The disease becomes more difficult to treat at each relapse, and if a patient does not respond or relapses during or within 6 months of MabThera -containing treatment, they will likely need a different treatment. These people often have a poor prognosis and few treatment options.5

With this approval, Gazyvaro is now approved in Europe to treat two common types of blood cancer. Gazyvaro was previously approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL) and comorbidities that make them unsuitable for full-dose fludarabine based therapy. That approval was based on data from the pivotal CLL11 study, where the combination of Gazyva/Gazyvaro plus chlorambucil showed superior efficacy when compared head-to-head with MabThera/Rituxan plus chlorambucil and chlorambucil alone.

Gazyvaro is marketed as Gazyva outside of the EU and Switzerland. As announced in February this year, Gazyva received approval by the US Food and Drug Administration in combination with bendamustine followed by Gazyva alone as a treatment for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment, based on the results of the GADOLIN study.

About the GADOLIN study
GADOLIN (NCT01059630; GA04753g) is a phase III open-label, multicentre, randomised two-arm study evaluating Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone until disease progression or for up to two years compared to bendamustine alone. GADOLIN included 396 patients with indolent (slow-growing) non-Hodgkin lymphoma (NHL), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response (CR), partial response (PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:
The Gazyva/Gazyvaro regimen improved PFS compared to bendamustine alone, as assessed by IRC (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001). Median PFS was not reached in those receiving the Gazyva/Gazyvaro regimen versus 13.8 months in those receiving bendamustine alone.

Investigator-assessed PFS was consistent with IRC-assessed PFS. As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001).

The Gazyva/Gazyvaro regimen reduced the risk of death (OS) by 38 percent compared to bendamustine alone based on a post-hoc analysis eight months after the primary analysis (HR=0.62, 95 percent CI 0.39-0.98). The median OS has not yet been reached in either study arm.

The most common Grade 3-4 adverse events that occurred more often (at least 2 percent or greater) in those receiving the Gazyva/Gazyvaro regimen compared to those receiving bendamustine alone were low white blood cell count (33 percent vs. 26 percent), infusion-related reactions (11 percent vs. 6 percent) and urinary tract infection (3 percent vs. 0 percent), respectively.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva/Gazyvaro is currently approved in more than 70 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia. The approval was based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil and chlorambucil alone. Gazyva was also recently approved by the U.S. Food and Drug Administration in combination with bendamustine followed by Gazyva alone for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment based on the results of the GADOLIN study. Gazyvaro is marketed as Gazyva outside of the EU and Switzerland.

As recently announced, the phase III GALLIUM study in people with previously untreated follicular lymphoma met its primary endpoint early. GALLIUM compared the efficacy and safety of Gazyva/Gazyvaro plus chemotherapy (CHOP, CVP or bendamustine) followed by Gazyva/Gazyvaro alone, head-to-head with MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan alone. Results from a pre-planned interim analysis showed that Gazyva/Gazyvaro-based treatment resulted in superior progression-free survival compared to MabThera/Rituxan-based treatment. Adverse events with either Gazyva/Gazyvaro or MabThera/Rituxan were consistent with what was seen in previous clinical trials when each was combined with various chemotherapies. Data from the GALLIUM study will be presented at an upcoming medical meeting and submitted to health authorities for approval consideration.
Gazyva/Gazyvaro is being studied in a large clinical programme, including the phase III GOYA study. GOYA is comparing Gazyva/Gazyvaro head-to-head with MabThera/Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL). Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed this type of NHL2. It is estimated that each year, more than 75,000 people are diagnosed with follicular lymphoma worldwide2.

Loxo Oncology Accepts Invitation to Present LOXO-101 to the FDA’s Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee

On June 15, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has accepted an invitation from the U.S. Food and Drug Administration (FDA) to participate in a meeting of the Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee on June 29, 2016 (Press release, Loxo Oncology, JUN 15, 2016, View Source [SID:1234513370]). The purpose of the meeting is to improve and encourage the development of oncology and hematology drugs for pediatric use. These meetings are held regularly by the FDA, with various invited sponsors. At the meeting, Loxo Oncology plans to present an overview of LOXO-101, with an emphasis on opportunities for pediatric development.

Background material for this meeting will be available on the FDA website approximately 2 days prior to the meeting.

Clinical Development of LOXO-101 in Pediatric Cancers

Loxo Oncology is conducting an ongoing Phase 1 multicenter, open-label clinical trial in pediatric patients with advanced solid or primary CNS tumors. In order to meet the criteria for enrollment, patients must be between one year of age and 21 years of age with a locally advanced or metastatic solid tumor or primary CNS tumor that has progressed, or was nonresponsive to available therapies, and for which no standard or available curative therapy exists. Patients at least one month old are eligible for enrollment if they have a diagnosis of infantile/congenital fibrosarcoma or congenital mesoblastic nephroma, with a documented NTRK fusion that has progressed, or was nonresponsive to available therapies, and for whom no standard or available curative therapy exists. The primary endpoint of the trial is to explore the safety of LOXO-101. Secondary endpoints include the characterization of pharmacokinetic properties, the identification of the maximum tolerated dose and/or the Phase 2 dose, a description of antitumor activity and a description of pain and health related quality of life impact.

In April 2016, Loxo Oncology announced the publication of a case report in the online edition of Pediatric Blood and Cancer, co-authored with Nemours Children’s Hospital, Northwestern University and St. Jude Children’s Research Hospital, describing a partial response in the first patient with a TRK fusion cancer enrolled in the pediatric Phase 1 dose-escalation trial of LOXO-101. The 16-month old female patient with advanced infantile fibrosarcoma (IFS), a rare pediatric cancer, experienced a 90 percent tumor regression, and repeat scans showed continued decrease in tumor volume. As of the preparation of the manuscript, the patient was in study cycle 5 with a RECIST confirmed partial response, and was beginning to achieve normal developmental milestones.

LOXO-101 has shown objective partial responses in adult patients with tumors harboring TRK gene fusions in a Phase 1 trial. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in adult patients with solid tumors that harbor TRK gene fusions.

About LOXO-101
LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions and a Phase 1 trial in pediatric patients. For additional information about the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov or www.loxooncologytrials.com. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.