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Vertex Reports First Quarter 2015 Financial Results

On April 29, 2015 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the quarter ended March 31, 2015 (Filing, Q1, Vertex Pharmaceuticals, APR 29, 2015, View Source [SID:1234506609]). Vertex also reiterated its financial guidance for total 2015 KALYDECO revenues and non-GAAP operating expenses.

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"We continue to make significant progress toward our goals of bringing new medicines to more people with CF and positioning the company for long-term growth," said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. "The number of people eligible for Kalydeco continues to increase with both geographic and label expansion, and we are also preparing for the potential launch of Orkambi, which we announced today as the proposed tradename for the combination of lumacaftor and ivacaftor. Our New Drug Application for Orkambi is currently under review by the FDA, and if approved, Orkambi would be the first medicine to treat the underlying cause of CF for eligible patients ages 12 and older with two copies of the F508del mutation – some 8,500 people in the U.S."

First Quarter 2015 Non-GAAP Financial Results

The non-GAAP financial results for the first quarter 2015 and first quarter 2014 exclude stock-based compensation expense, costs related to the relocation of the company’s corporate headquarters, hepatitis C-related revenues and costs and other adjustments.

Total Non-GAAP Revenues: Total non-GAAP revenues for the first quarter of 2015 were $135.4 million, including $130.2 million in net product revenues from KALYDECO and $5.3 million from royalty revenues.

Net Product Revenues from KALYDECO: Vertex’s first quarter 2015 net product revenues from KALYDECO were $130.2 million compared to $99.5 million for the first quarter of 2014. The increased KALYDECO net product revenues, compared to the first quarter of 2014, resulted primarily from additional people being treated with KALYDECO in both U.S. and ex-U.S. markets.
Non-GAAP Cost of Product Revenues and Royalty Expenses (COR): Total combined non-GAAP COR expenses for the first quarter of 2015 were $10.7 million, compared to $9.6 million for the first quarter of 2014.

Non-GAAP Research and Development (R&D) Expenses and Sales, General and Administrative (SG&A) Expenses: Total combined non-GAAP R&D and SG&A expenses for the first quarter of 2015 were $246.3 million, compared to $233.9 million for the first quarter of 2014. The components include:

R&D Expenses: Non-GAAP R&D expenses were $177.2 million for the first quarter of 2015, compared to $181.5 million in non-GAAP R&D expenses for the first quarter of 2014. The R&D expenses for the first quarter of 2015 were similar to the first quarter of 2014 as a result of the completion of the Phase 3 program for the combination of lumacaftor and ivacaftor in the first half of 2014, offset by increased costs related to the initiation of the pivotal Phase 3 program for VX-661 in combination with ivacaftor in the first quarter of 2015.
SG&A Expenses: Non-GAAP SG&A expenses were $69.1 million for the first quarter of 2015, compared to $52.4 million in non-GAAP SG&A expenses for the first quarter of 2014. This increase was primarily the result of increased investment in global commercial support for the planned launch of ORKAMBI (lumacaftor/ivacaftor).
Non-GAAP Net Loss Attributable to Vertex: Vertex’s first quarter 2015 non-GAAP net loss was $148.4 million, or $0.62 per diluted share, compared to a non-GAAP net loss of $151.4 million, or $0.65 per diluted share, for the first quarter of 2014. The non-GAAP net loss for the first quarter of 2015 was similar to the first quarter of 2014 as a result of increased KALYDECO product revenues, offset by increased operating expenses and interest expense.

Cash Position at March 31, 2015

As of March 31, 2015, Vertex had $1.2 billion in cash, cash equivalents and marketable securities compared to $1.4 billion in cash, cash equivalents and marketable securities as of December 31, 2014. As of March 31, 2015, Vertex had $300 million outstanding from a credit agreement that provides for a secured loan of up to $500 million.

2015 Financial Guidance

This section contains forward-looking guidance about the financial outlook for Vertex.

Vertex today reiterated its financial guidance for total 2015 KALYDECO revenues and non-GAAP operating expenses:

KALYDECO Net Revenues: Vertex expects KALYDECO net revenues of $560 to $580 million for 2015.
Non-GAAP R&D and SG&A Expenses: Vertex expects that its combined non-GAAP R&D and SG&A expenses in 2015 will be in the range of $1.05 to $1.10 billion.
Vertex’s expected combined non-GAAP R&D and SG&A expenses exclude stock-based compensation expense and certain other expenses recorded in 2015.

Non-GAAP Financial Measures

In this press release, Vertex’s financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results exclude stock-based compensation expense, costs related to the relocation of the company’s corporate headquarters, hepatitis C-related revenues and costs and other adjustments. These results are provided as a complement to results provided in accordance with GAAP because management believes these non-GAAP financial measures help indicate underlying trends in the company’s business, are important in comparing current results with prior period results and provide additional information regarding the company’s financial position. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally and to manage the company’s business and to evaluate its performance. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the attached financial information.

First Quarter 2015 GAAP Financial Results

Total Revenues: Total revenues for the first quarter of 2015 were $138.5 million compared with $118.5 million in total revenues for the first quarter of 2014. First quarter 2015 revenues were comprised primarily of $130.2 million in KALYDECO net product revenues and an aggregate of $8.3 million in net product revenues from INCIVEK, royalty revenues and collaborative revenues. For the first quarter of 2014, Vertex reported $99.5 million in net product revenues from KALYDECO and an aggregate of $18.9 million in net product revenues from INCIVEK, royalty revenues and collaborative revenues.

Operating Costs and Expenses: Total operating costs and expenses for the first quarter of 2015 were $310.5 million, including certain charges of $53.5 million, compared to $334.5 million for the first quarter of 2014, including certain charges of $91.0 million. GAAP operating costs and expenses include:

COR Expenses: COR expenses were $12.3 million for the first quarter of 2015, including $1.6 million of certain charges, compared to $15.5 million for the first quarter of 2014, including $5.9 million of certain charges.
R&D Expenses: R&D expenses were $215.6 million for the first quarter of 2015, including $38.4 million of certain charges, compared to $238.6 million for the first quarter of 2014, including $57.1 million of certain charges.
SG&A Expenses: SG&A expenses were $85.9 million for the first quarter of 2015, including $16.7 million of certain charges, compared to $74.2 million for the first quarter of 2014, including $21.8 million of certain charges.
Net Loss Attributable to Vertex: Vertex’s first quarter 2015 net loss was $198.6 million, or $0.83 per diluted share, including net charges of $50.2 million. Vertex’s first quarter 2014 net loss was $232.5 million, or $1.00 per diluted share, including net charges of $81.1 million.

Note 1: For the three months ended March 31, 2014, the company presents the effect of its relationship with Alios, which it consolidated as a variable interest entity from June 2011 to December 2013, as discontinued operations attributable to Vertex in its condensed consolidated statements of operations.

Note 2: In the three months ended March 31, 2015, "Real estate restructuring costs" consisted of restructuring credits of $3.6 million primarily related to the company’s relocation from Cambridge to Boston, Massachusetts. In the three months ended March 31, 2014, "Real estate restructuring costs" consisted of (i) transition costs related to the company’s relocation that were recorded as R&D and SG&A, and (ii) restructuring charges related to this relocation.

Note 3: In the three months ended March 31, 2015, "HCV related revenues and costs" consisted of (i) $0.7 million net product revenues from INCIVEK, (ii) $1.5 million royalty revenues from INCIVO, (iii) $0.6 million HCV collaborative revenues, (iv) $1.6 million COR expenses, (v) R&D and SG&A credits (including the pharma fee) and (vi) $0.2 million restructuring expenses. In the three months ended March 31, 2014, "HCV related revenues and costs" included in the company’s loss from continuing operations consisted of (1) $3.9 million net product revenues from INCIVEK, (2) $4.9 million royalty revenues from INCIVO, (3) $1.4 million HCV collaborative revenues, (4) $0.7 million and $5.2 million costs of product revenues and royalty revenues related to INCIVEK and INCIVO, respectively, (5) R&D and SG&A expenses (including the pharma fee) and (6) $0.6 million restructuring expenses.

Note 4: In each of the three months ended March 31, 2014 and 2015, "Other adjustments" consisted of development cost associated with VX-509. In addition, in the three months ended March 31, 2015, "Other adjustments" included amounts related to a variable interest entity.

Note 5: In each of the three months ended March 31, 2014 and 2015, the company excludes from its non-GAAP loss attributable to Vertex restructuring (income) expenses. In addition, in the three months ended March 31, 2014 discontinued operations are excluded from its non-GAAP loss attributable to Vertex.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO (ivacaftor)

Ivacaftor is a cystic fibrosis transmembrane conductance regulatory (CFTR) potentiator indicated for the treatment of cystic fibrosis (CF). In the U.S. (in patients age 2 years and older) and Europe (in patients age 6 years and older), ivacaftor is indicated for patients who have one of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. In Canada (in patients 6 years and older), ivacaftor is indicated for patients with these same mutations and also for patients with the G970R mutation. Additionally, in the U.S. (in patients age 2 years and older) and Canada (in patients age 18 years and older) ivacaftor is indicated for the treatment of CF in patients who have an R117H mutation in the CFTR gene.

Ivacaftor is available as 150 mg tablets in countries where it is approved for patients age 6 years and older, and additionally in the U.S. as 50 mg and 75 mg oral granules for patients age 2 to less than 6 years.

Ivacaftor is not effective in patients with CF with 2 copies of the F508del mutation (F508del/F508del) in the CFTR gene. The safety and efficacy of ivacaftor in children with CF younger than 2 years of age have not been studied. The use of ivacaftor in children under the age of 2 years is not recommended.

High liver enzymes (transaminases; ALT and AST) have been reported in patients with CF receiving ivacaftor. Transaminase elevations were more common in patients with a history of transaminase elevations or in patients who had abnormal transaminases at baseline. It is recommended that ALT and AST be assessed prior to initiating ivacaftor, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring of liver function tests should be considered. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal. Following resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing.

Use of ivacaftor with medicines that are strong CYP3A inducers, such as the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John’s wort, substantially decreases exposure of ivacaftor and may diminish effectiveness. Therefore, co-administration is not recommended. The dose of ivacaftor must be adjusted when used concomitantly with strong and moderate CYP3A inhibitors or when used in patients with moderate or severe hepatic disease.

Cases of non-congenital lens opacities/cataracts have been reported in pediatric patients treated with ivacaftor. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating ivacaftor treatment.

Serious adverse reactions that occurred more frequently with ivacaftor included abdominal pain, increased liver enzymes, and low blood sugar (hypoglycemia). The most common side effects associated with ivacaftor include headache; upper respiratory tract infection (common cold), including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness. These are not all the possible side effects of ivacaftor. A list of the adverse reactions can be found in the product labeling for each country where ivacaftor is approved. Patients should tell their healthcare providers about any side effect that bothers them or does not go away.

U.S. Food and Drug Administration Accepts Supplemental Biologics License Application for Opdivo (nivolumab) in Patients with Previously Untreated Advanced Melanoma

On April 29, 2015 Bristol-Myers Squibb reported that the U.S. Food and Drug Administration (FDA) has accepted for filing and review the supplemental Biologics License Application (sBLA) for Opdivo (nivolumab) for the treatment of previously untreated patients with unresectable or metastatic melanoma (Press release, Bristol-Myers Squibb, APR 29, 2015, View Source [SID:1234503222]). The FDA also granted Priority Review for this application. The projected FDA action date is August 27, 2015.

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Opdivo was first approved by the FDA in December 2014 for patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This initial indication was approved under accelerated approval based on tumor response rate and durability of response from CheckMate -037 clinical trial results. This new sBLA accepted by the FDA includes data from CheckMate -066, which evaluated Opdivo in treatment naïve patients with BRAF wild-type advanced melanoma as compared to dacarbazine chemotherapy (DTIC). In the trial, safety and tolerability were well-characterized with fewer treatment-related Grade 3/4 adverse events observed with Opdivo than dacarbazine.

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"The CheckMate -066 trial marked the first time that a PD-1 immune checkpoint inhibitor showed a survival benefit in a randomized Phase III trial," said Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. "We look forward to continuing to work with the FDA to ensure cancer patients are provided the latest clinical advances that have the potential for improved responses and long-term survival."

About Advanced Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to the other organs, such as the lymph nodes, lungs, brain or other areas of the body. The incidence of melanoma has been increasing for at least 30 years. In 2015, an estimated 73,870 melanoma cases will be diagnosed in the U.S. Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate is just 6 months with a 1-year survival of 25.5%, making it one of the most aggressive forms of cancer.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that has received approval from the U.S. FDA as a monotherapy in two cancer indications. On March 5, 2015, Opdivo received FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

In the U.S., Opdivo is also indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Opdivo became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma.

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide.

Immuno-Oncology at Bristol-Myers Squibb

Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.

To address this unmet medical need, Bristol-Myers Squibb is leading research in an innovative field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different pathways in the treatment of cancer.

Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical, Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

Severe pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience in 691 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.7% (5/691) of patients receiving OPDIVO; no cases occurred in Trial 1. In Trial 1, pneumonitis, including interstitial lung disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients receiving OPDIVO; one with Grade 3 and five with Grade 2. Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO until resolution for Grade 2.

Immune-Mediated Colitis

In Trial 1, diarrhea or colitis occurred in 21% (57/268) of patients receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy. Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving OPDIVO; five with Grade 3 and one with Grade 2. Monitor patients for immune-mediated colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or recurrent colitis upon restarting OPDIVO.

Immune-Mediated Hepatitis

In Trial 1, there was an increased incidence of liver test abnormalities in the OPDIVO-treated group as compared to the chemotherapy-treated group, with increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1% (3/268) of patients receiving OPDIVO; two with Grade 3 and one with Grade 2. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated hepatitis.

Immune-Mediated Nephritis and Renal Dysfunction

In Trial 1, there was an increased incidence of elevated creatinine in the OPDIVO-treated group as compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction occurred in 0.7% (2/268) of patients. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 serum creatinine elevation, withhold OPDIVO and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue OPDIVO. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue OPDIVO.

Immune-Mediated Hypothyroidism and Hyperthyroidism

In Trial 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. Monitor thyroid function prior to and periodically during treatment. Administer hormone replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred in less than 2% of OPDIVO-treated patients: adrenal insufficiency, uveitis, pancreatitis, facial and abducens nerve paresis, demyelination, autoimmune neuropathy, motor dysfunction, and vasculitis. Across clinical trials of OPDIVO administered at doses 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: hypophysitis, diabetic ketoacidosis, hypopituitarism, Guillain-Barré syndrome, and myasthenic syndrome. Based on the severity of adverse reaction, withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone- replacement therapy.

Embryofetal Toxicity

Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

Serious adverse reactions occurred in 41% of patients receiving OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

Common Adverse Reactions

The most common adverse reaction (≥20%) reported with OPDIVO was rash (21%).
Please see US Full Prescribing Information for OPDIVO.

8-K – Current report

On April 29, 2015 Bellicum Pharmaceuticals reported it has entered into a license agreement with Leiden University Medical Center (LUMC), Netherlands, for worldwide rights to develop, manufacture and commercialize high-affinity TCR (T cell receptor) product candidates targeting solid tumors expressing the preferentially-expressed antigen in melanoma, or PRAME (Filing, 8-K, Bellicum Pharmaceuticals, APR 29, 2015, View Source [SID:1234503221]).

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TCRs are engineered T cells that are activated when in the presence of target antigens in cancer cells. The lead TCRs under this license agreement have been shown to have a high affinity to PRAME, a cancer antigen that is preferentially expressed in melanomas, sarcomas, neuroblastomas and other solid tumors, but generally not expressed in normal tissue.

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Bellicum’s first TCR product candidate under this agreement, BPX-701, targets PRAME and is expected to enter Phase 1/2 clinical trials before the end of 2015. BPX-701 incorporates Bellicum’s proprietary safety mechanism, CaspaCIDe, for improved control over the cells.

Bellicum also exclusively licensed LUMC’s TCR technology targeting POU-2AF1. These TCRs have a high affinity to the B cell transcription factor expression product of POU-2AF1, which is present in primary chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), mantle cell lymphoma and multiple myeloma.

"TCRs are demonstrating broad potential for the treatment of solid tumors," said Tom Farrell, President and Chief Executive Officer of Bellicum Pharmaceuticals. "The cancer targets under this license, combined with our CaspaCIDe safety mechanism, form the basis of a growing portfolio of differentiated T cell therapies with the potential to address a wide range of cancers."

OncoMed Highlights Immuno-Oncology Discoveries During 2015 Research & Development Day

On April 29, 2015 OncoMed reported new discoveries related to the company’s anti-cancer immuno-oncology pipeline during the company’s first Research and Development (R&D) Day for analysts and investors (Press release, OncoMed, APR 29, 2015, View Source [SID:1234503219]).

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"OncoMed has always been focused on developing transformative anti-cancer therapeutics, and the drug discovery efforts we apply to every program have led us to identify some truly first-in-class candidates targeting fundamental cancer stem cell and immuno-oncology pathways," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "During today’s R&D Day event, we showcased the clinical, translational medicine and research science taking place at OncoMed, unveiled emerging programs that haven’t yet been in the spotlight, and provided an in-depth understanding of the way we think about drug discovery and development across our portfolio."

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Among the highlights of OncoMed’s R&D Day were data from a series of experiments that identified a novel immune therapy mechanism for demcizumab (anti-DLL4, OMP-21M18) and demonstrated synergistic activity when anti-DLL4 is combined with an anti-PD1 checkpoint inhibitor. Anti-DLL4 modulates T-cell response by reducing the accumulation of monocytic myeloid-derived suppressor cells, a key population of immunosuppressive cells that inhibit anti-tumor immune responses that are otherwise not addressed by anti-PD1 therapy. When anti-DLL4 is combined with anti-PD1, researchers observed increased inhibition of tumor growth and more robust anti-tumor immune responses in immunocompetent xenograft models as compared to either agent alone. Further, the combination of anti-DLL4 and anti-PD1 reduced tumor growth in re-implantation experiments. These results indicate that dual targeting of DLL4 and PD1 may promote effective and durable cancer therapy by increasing anti-tumor immune response and long-term immunological memory. This research could provide the foundation for a novel clinical development strategy. These data were recently presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

A new approach, discovered by OncoMed researchers, to inhibit a known immune-oncology receptor was also disclosed publicly for the first time. GITR, a member of the tumor necrosis factor family, is known to be an important receptor in T-cell activation and regulation. OncoMed scientists have devised a novel strategy for the creation of robust T cell activating agents that utilizes fully human single-gene GITRL trimeric ligand attached to an antibody framework. The unique design of OncoMed’s proprietary strategy also enables the creation of novel bispecific agents. In preclinical studies, OncoMed’s GITRL-Fc candidate results in a potent anti-tumor immune response.

A third example of OncoMed’s immuno-oncology research efforts revealed the discovery of a novel and previously "missing" checkpoint target. Tumor cells are believed to take advantage of the immune system’s so called "checkpoints" to escape detection. While significant advances have been made in the understanding of checkpoint inhibitors, a number of orphan targets exist and these have been the subject of extensive research by OncoMed scientists for several years. One outcome of these efforts is discovery of a receptor (nicknamed "PD2"), which appears to be an activating receptor for the known checkpoint inhibitor PD-L2. Initial research by OncoMed demonstrates that "PD2" mediates important immunological functions associated with PD-L2. Activation of PD-L2 may provide an entirely new pathway by which to engage the body’s own immune system in combatting tumor cells.

In addition, OncoMed’s 2015 R&D Day included presentations of recently updated clinical data for demcizumab and tarextumab (anti-Notch2/3, OM59R5) that represent the foundation for the company’s four ongoing randomized Phase 2 clinical trials. Additionally, clinical and preclinical proof-of-concept data were presented for two of the company’s biomarker assays in development, and overview of OncoMed’s approach to elucidating cancer biology to identify and validate new leads and inform clinical trial design.

OncoMed’s 2015 R&D Day also featured special guest speakers. Manuel Hidalgo, MD, PhD, Vice Director of Translational Research, Spanish National Cancer Research Centre (CNIO), shared his experience as an investigator in the company’s demcizumab clinical trials in pancreatic cancer. Jorge DiMartino, MD, PhD, Vice President, Translational Development of Celgene Corporation provided a presentation on Celgene’s multi-product collaboration with OncoMed and the research that initially piqued Celgene’s interest.

A webcast of the R&D Day presentations can be accessed under the Investor Relations section of the company’s website (www.oncomed.com). A replay of the webcast will be archived on the OncoMed website for approximately 60 days following the presentation.

Amgen To Discuss Details Of The Biologics License Application For Talimogene Laherparepvec For Patients With Metastatic Melanoma

On April 29, 2015 Amgen reported that it will discuss the data supporting the Biologics License Application (BLA) for talimogene laherparepvec monotherapy for the treatment of patients with injectable regionally or distantly metastatic melanoma at today’s joint meeting of the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) and Oncologic Drugs Advisory Committee (ODAC)
(Press release, Amgen, APR 29, 2015, View Source [SID:1234503213]).

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At the meeting, Amgen will present the results of the pivotal Phase 3 OPTiM study, which showed that talimogene laherparepvec monotherapy is the first oncolytic immunotherapy to demonstrate therapeutic benefit in a Phase 3 pivotal trial for patients with metastatic melanoma.

"The incidence of melanoma, the most serious form of skin cancer, has continued to rise over the last 30 years, even as many other cancers are in decline," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Despite recent advances, there is still an unmet need in this disease. For this reason, today’s discussion about talimogene laherparepvec for the treatment of patients with metastatic melanoma is important. If approved, this novel agent could provide physicians and patients with an additional treatment option for this disease."

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with granulocyte-macrophage colony-stimulating factor (GM-CSF), which can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.

Amgen has in place a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

According to the American Cancer Society, with an estimated 74,000 new melanoma diagnoses and nearly 10,000 deaths this year1, melanoma remains a significant public health concern in the U.S. Additionally, metastatic melanoma continues to be one of the most difficult to treat cancers because it is highly aggressive and complex. Despite recent treatment advances, the five-year survival rate for melanoma is only 20 percent2, so additional safe and effective treatment options are needed.

OPTiM Study Design and Results
Study 005/05, referred to as OPTiM, was a Phase 3, multicenter, open-label, randomized clinical trial comparing talimogene laherparepvec to GM-CSF in patients with advanced melanoma (stage IIIB, IIIC, or IV) that was not surgically resectable. The primary endpoint of the study was durable response rate (DRR).

In the 436-patient study, talimogene laherparepvec significantly improved DRR with 16.3 percent of talimogene laherparepvec patients achieving a complete response (CR) or partial response (PR) within the first 12 months of treatment and maintaining it continuously for at least six months compared to 2.1 percent of patients treated with GM-CSF (p <0.001).

The OPTiM study also provided additional secondary and exploratory data that demonstrated the effects of talimogene laherparepvec in patients with Stage III/IV metastatic melanoma, including:

Improved overall (CR + PR) response rate compared with GM-CSF, 26.4 percent vs. 5.7 percent, respectively. In particular, the CR rate was higher in the talimogene laherparepvec arm than in the GM-CSF arm (10.8 percent vs. 0.7 percent, respectively).

A strong trend in overall survival (OS). The median OS was 4.4 months longer in the talimogene laherparepvec arm than in the GM-CSF arm (hazard ratio: 0.79; p=0.051).

Evidence of a systemic effect. Eight of 71 patients (11.3 percent) with visceral lesions that could not be injected (predominately in the lung and liver) had an overall decrease in those lesions of more than 50 percent.

The most commonly reported treatment-related adverse events were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection-site pain. Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common serious adverse reaction was cellulitis.