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ARIAD Reports Third Quarter 2015 Financial Results and Progress on Strategic Objectives

On November 3, 2015 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported financial results for the third quarter of 2015, including revenue from sales of Iclusig (ponatinib) (Press release, Ariad, NOV 3, 2015, View Source;p=RssLanding&cat=news&id=2105752 [SID:1234507898]). The Company also provided an update on key corporate initiatives and clinical-trial plans.

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"We are on track to achieve our product revenue guidance of $130 to $140 million for 2015, with important contributions coming from European and U.S. sales and anticipated successful resolution of pricing negotiations for Iclusig in France," stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. "Each of the major clinical initiatives – outlined at the beginning of 2015 as part of our three-year strategic operating plan – is progressing as projected. These include full patient enrollment in the ALTA pivotal trial of brigatinib, ongoing enrollment of patients in the dose-ranging OPTIC trial of Iclusig and anticipated initiation before year-end of the second-line trial of Iclusig. We expect that results from these randomized trials, if positive, will form the basis for expanded utilization of Iclusig and initial approval of brigatinib. We are also moving ahead with another randomized trial – a comparison of brigatinib and crizotinib in front-line non-small cell lung cancer – which we anticipate beginning in the first half of next year."

2015 Third Quarter Financial Results

Revenues

Net product revenues from sales of Iclusig were $27.5 million for the third quarter, compared to $14.5 million in the third quarter of 2014 and $27.8 million in the second quarter of 2015.

U.S. sales of Iclusig were $20.3 million for the third quarter, compared to $21.6 million in the second quarter of 2015, the difference primarily due to flat quarter-over-quarter demand and an increase in gross-to-net adjustments.

European sales of Iclusig were $7.2 million for the third quarter, compared to $6.2 million in the second quarter of 2015, the difference primarily due to increased quarter-over-quarter demand.

Shipments of Iclusig to patients in France were $2.2 million for the third quarter of 2015. Cumulative total shipments in France totaled $23.3 million through September 30, 2015. We will record revenue related to cumulative shipments in France upon completion of pricing and reimbursement negotiations in France, net of any amounts that will be refunded to the French health authorities as a result of these negotiations, which we anticipate will be completed by year-end 2015.

Operating Expenses

Research and development (R&D) expenses were $48.2 million for the third quarter of 2015, an increase of 75% compared to the third quarter of 2014. This reflects an increase in costs for our ongoing Phase 2 ALTA trial of brigatinib, and NDA-enabling pharmacology and manufacturing activities, costs related to the initiation of the Iclusig Phase 2 dose-ranging OPTIC trial, as well as an increase in personnel and other costs in support of our continuing R&D activities.
Selling, general and administrative (SG&A) expenses were $36.7 million for the third quarter of 2015, an increase of 9% compared to the third quarter of 2014. This reflects an increase in personnel costs, including the impact of severance costs associated with the pending retirement of our chief executive officer and an increase in costs in support of expanding distribution and sales of Iclusig.

Net Loss

Net loss for the quarter ended September 30, 2015 was $55.5 million, or $0.29 per share, compared to a net loss of $50.1 million, or $0.27 per share, for the same period in 2014.
During the quarter ended September 30, 2015, we recorded in marketable securities on our balance sheet the value of shares of common stock we own in REGENXBIO, Inc., which completed an initial public offering during the quarter; these shares are not saleable until the first quarter of 2016. The value of the shares at September 30, 2015 was $15.1 million. The value net of tax, $9.1 million, is recorded in other comprehensive income. An intra-period tax benefit of $6.0 million related to the tax consequences of this item included in other comprehensive income is recorded as a tax benefit in our statement of operations.

Cash Position

As of September 30, 2015, cash and cash equivalents totaled $282.2 million, compared to $352.7 million at December 31, 2014.
During the quarter ended September 30, 2015, we entered into a royalty financing agreement with PDL BioPharma, Inc. (PDL) under which we received $50 million from PDL in exchange for payments to PDL based on a percentage of global sales of Iclusig over time until PDL receives a 10% internal rate of return. In July 2016, we will receive an additional $50 million from PDL. Under the agreement, we also have an option, in our sole discretion, to receive up to an additional $100 million through July 2016.
Recent Progress and Key Objectives

Commercialization of Iclusig

Approximately 125 new patients were treated with Iclusig in the U.S. during the third quarter of 2015. Importantly, approximately 55% of these new patients receiving Iclusig are patients with chronic-phase chronic myeloid leukemia (CP-CML).
Through the third quarter, there have been approximately 980 unique prescribers of Iclusig in the U.S., an increase in the cumulative prescriber base of approximately 13% from the second quarter of 2015.
In Europe, we are now promoting Iclusig in 12 countries: the United Kingdom, France, Germany, Italy, Austria, Switzerland, The Netherlands, Luxembourg, Denmark, Norway, Sweden, and Finland. In addition, Iclusig is available for purchase and is being supplied through named-patient programs and prior authorizations in Spain, Portugal, Ireland, Turkey and in several markets in Eastern Europe.

Iclusig is now reimbursed in Canada and Australia, and commercial launches continue in both countries through our regional distribution partners.

Iclusig Clinical Development

In August, we initiated patient enrollment in the OPTIC (Optimizing Ponatinib Treatment In CML) trial of Iclusig. This randomized, dose-ranging trial is designed to evaluate three different starting doses of ponatinib in patients with refractory CP-CML and is expected to inform the optimal use of Iclusig in these patients. Approximately 450 patients will be enrolled at clinical sites around the world.

Later this quarter, we expect to begin a Phase 3 trial of Iclusig in patients with CP-CML, who have experienced treatment failure after imatinib therapy. This second-line study of Iclusig is expected to enroll approximately 600 patients and is aimed at expanding the indication for Iclusig in patients with resistant and intolerant CML.

Brigatinib Clinical Development

In September, we achieved full patient enrollment in the pivotal Phase 2 ALTA trial of brigatinib. This registration study enrolled approximately 220 patients at 71 sites in North America, Europe and Asia. We are on track to file in the third quarter of 2016 for approval of brigatinib in the U.S.

The randomized front-line clinical trial of brigatinib is expected to begin in the first half of 2016. This Phase 3 trial will compare brigatinib and crizotinib in approximately 300 patients with ALK+ non-small cell lung cancer (NSCLC), who have not received prior ALK inhibitors.

Advancing the Pipeline

We are on track to file an investigational new drug (IND) application for AP32788 by year-end 2015 and to begin a Phase 1/2 proof-of-concept clinical trial in 2016. AP32788 is an orally active tyrosine-kinase inhibitor (TKI), which has a unique profile against a validated class of mutated targets in NSCLC and certain other solid tumors and may address an important unmet medical need.
Today’s Conference Call at 8:30 a.m. ET

We will hold a live webcast and conference call of our third quarter 2015 financial results this morning at 8:30 a.m. ET. The live webcast can be accessed by visiting the investor relations section of the Company’s website at View Source The call can be accessed by dialing 888-311-8173 (domestic) or 330-863-3376 (international) five minutes prior to the start time and providing the pass code 55634805. A replay of the call will be available on the ARIAD website approximately two hours after completion of the call and will be archived for three weeks.

About Iclusig (ponatinib) tablets

Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug-design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

Iclusig is approved in the U.S., EU, Australia, Switzerland, Israel and Canada.

In the U.S., Iclusig is a kinase inhibitor indicated for the:

Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING

WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning

Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.

Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.

Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.

Please see the full U.S. Prescribing Information for Iclusig, including the Boxed Warning, for additional important safety information.

CBMG Responds to Inquiries from Investors and the Scientific Community About the Phase IIa Results from CAR-T CD20 Immuno-Oncology Clinical Development Program for Advanced B-cell Non-Hodgkin Lymphoma

On November 3, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective treatments for degenerative and cancerous diseases, reported that it has responded to inquiries from investors and the scientific community about the announced results from an ongoing Phase IIa clinical trial evaluating the safety, feasibility and anti-tumor activity of its acquired Chimeric Antigen Receptor-Modified T-Cells (CAR-T) immunotherapy (CBM-CD20.1) targeting CD20 for the treatment of patients with advanced B-cell Non-Hodgkin lymphoma (NHL) (Press release, Cellular Biomedicine Group, NOV 3, 2015, View Source [SID:1234507920]).

What are the significant treatment differences between the Phase I and Phase IIa studies?
The Phase IIa study excluded patients with uncontrolled bulky lymphoma (maximum diameter ≥5 cm or lesion number >3) after salvage treatments. The object of the early Phase IIa study is to evaluate the clinical activity of CBM-CD20.1 in NHL patients refractory or relapsed after chemotherapy. We also want to evaluate whether CBM-CD20.1 might improve the clinical outcome of advanced NHL patients that respond partially to chemotherapy. There will be a more detailed discussion in an upcoming manuscript in a peer-reviewed journal.

Please clarify how many patients actually enrolled in this Phase IIa NHL trial?
Fifteen patients were screened and twelve patients were enrolled. Of the twelve patients enrolled, two patients did not proceed with cell infusion. One withdrew consent and the other had disease progression and did not meet the inclusion criteria. Nine of the ten patients were refractory or relapsed after chemotherapy. The tenth patient showed partial response to most recent chemotherapy.

The abstract published by the 4th International Conference on Translational Medicine held in Baltimore on October 26-28th discussed an 11th patient from the Phase I trial. This patient remained in complete remission for over 25 months since the initial treatment of CBM-CD20.1, and the response is still on going. This patient was given a second treatment of CBM-CD20.1 infusions at 16 months post initial treatment based on the significant decrease of CD20 CAR-T cells in the peripheral blood ("Patient X"). In congruence with study protocol, we did not include Patient X in our presentation. The presented data of the 10 patients (seven patients with diffuse large B-cell lymphoma (DLBCL) and three patients with other types of NHL) from the Phase IIa trial can be viewed on the Company website under Investor Relations/Presentations.

How many of the patients who participated in the original Phase I trial enrolled in the Phase IIa study?None of the ten patients reported in the Company’s October 28th press release had participated in the original Phase I trial.

Please provide rationale on why the Phase II study result is substantially better than that of the Phase I study.
Besides excluding patients with uncontrolled bulky lymphoma, there were improvements in the conditioning regimen and treatment protocol, as well as the CBM-CD20.1 CART production process. Together these contributed to the improved clinical outcome in the phase IIa results.

What is the Company’s next step on targeting CD20 for the treatment of NHL?
The company intends to seek an opportunity to confirm the safety and clinical efficacy of CBM-CD20.1 in advanced NHL in a multicenter, single arm, Phase IIb trial. We plan to also explore other opportunities such as repeated treatment of CBM-CD20.1 or combination with other immuno-oncology therapies in advanced NHL.

Bristol-Myers Squibb and the Johns Hopkins Kimmel Cancer Center Enter Into a Collaboration Agreement as Part of U.S. Immuno-Oncology Rare Population Malignancy Research Program

On November 3, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported that they have entered into a collaboration agreement with The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins as part of Bristol-Myers Squibb’s Immuno-Oncology Rare Population Malignancy (I-O RPM) program in the U.S (Press release, Bristol-Myers Squibb, NOV 3, 2015, View Source [SID:1234507919]). The I-O RPM research program is a multi-institutional initiative with academic-based cancer centers focused on the clinical investigation of immuno-oncology therapeutics as potential treatment options for patients with high risk, poor prognostic cancers, defined as a rare population malignancy.

As part of the I-O RPM program, Bristol-Myers Squibb and the Johns Hopkins Kimmel Cancer Center will conduct a range of early phase clinical studies and Bristol-Myers Squibb will fund positions within The Johns Hopkins University School of Medicine fellowship program.

"Johns Hopkins has been a long-time collaborator with Bristol-Myers Squibb in immuno-oncology research," said Laura Bessen, M.D., head of U.S. Medical, Bristol-Myers Squibb. "We look forward to working with them as part of the I-O RPM research program as we continue to advance the science in this innovative field of cancer research and development, particularly among subpopulations of patients with high risk, poor prognostic cancers."

About I-O RPM

Immuno-oncology is an innovative approach to cancer research and treatment that is designed to harness the body’s own immune system to fight cancer. The I-O RPM research program focuses on significant areas of high unmet need marked by poor outcomes among patients with rare population malignancies. A rare population malignancy is a subpopulation within a higher incident disease population. These patients have aggressive disease with an increased potential for early metastasis to multiple sites and/or are initially refractory or subject to early recurrences with conventional cancer therapies. Existing clinical research provide a strong rationale for further research into the potential of immunotherapies for these cancers.

The I-O RPM research program is a multi-institutional initiative with Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medicine Developmental Therapeutics Institute, Moffitt Cancer Center and now the Johns Hopkins Kimmel Cancer Center. I-O RPM builds on Bristol-Myers Squibb’s formation in 2012 of the International Immuno-Oncology Network (II-ON), which is a global collaboration between Bristol-Myers Squibb and academia focused on facilitating the translation of scientific research findings into clinical trials and, eventually, clinical practice.

Threshold Pharmaceuticals Announces Preclinical Data on Combination of Evofosfamide With Immune Checkpoint Inhibitors to Be Presented at the SITC 2015 Meeting

On November 3, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported that preclinical data on the combination of evofosfamide with immune checkpoint inhibitors will be presented in a scientific poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in Maryland, November 4-8, 2015 (Press release, Threshold Pharmaceuticals, NOV 3, 2015, View Source [SID:1234507918]). Evofosfamide is Threshold’s investigational hypoxia-activated prodrug, which is currently the subject of two fully-enrolled Phase 3 clinical trials for which Threshold expects to announce top-line data around the end of 2015.

"This is an exciting time for the field of cancer immunotherapy, and continued progress will depend on a better understanding of the tumor microenvironment and finding novel combination therapies that are more effective than immunotherapy alone," said Michael A. Curran, Ph.D., Assistant Professor at the University of Texas M.D. Anderson Cancer Center and senior author on the scientific poster.

"Our research shows that hypoxia in the tumor microenvironment forms a barrier to T cell infiltration and fosters immunotherapy resistance in prostate cancer and other solid tumors," Curran said. "We found that evofosfamide-driven disruption of hypoxic zones sensitizes highly resistant prostate cancer models to treatment with immune checkpoint inhibitors anti-CTLA-4 and anti-PD-1."

Research conducted in Curran’s laboratory shows that hypoxic zones in prostate tumors resist infiltration by T cells, which are capable of attacking and killing tumor cells. In contrast, normoxic areas of the same tumor experience robust infiltration by T cells.

In mouse models of prostate cancer, Curran and colleagues show that combination therapy with evofosfamide and anti-CTLA-4/anti-PD-1 treatment opens up the hypoxic zones to T cell infiltration.

Furthermore, evofosfamide helps sensitize otherwise immunotherapy-resistant prostate tumors to anti-CTLA-4/anti-PD-1 therapy in models of prostate cancer as evidenced by the smallest tumor burdens on average being observed with combination therapy.

"This combination of hypoxia disruption and T cell checkpoint blockade has potential to render some of the most therapeutically resistant cancers sensitive to immunotherapy," Curran said.

"Combining with immunotherapy is an exciting possibility that fits well with our development strategy to maximize the potential therapeutic applications of evofosfamide," said Tillman Pearce, M.D., Chief Medical Officer at Threshold. "The data from Dr. Curran’s research suggests that combining evofosfamide with immune checkpoint inhibitors warrants further investigation."

The poster titled "Tumor hypoxia drives immune suppression and immunotherapy resistance" by Midan Ai et al. will be presented on Saturday, November 7, 2015, from 12:45 PM – 2:00 PM. The abstract is now available at View Source or by clicking here.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug that is thought to be activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Evofosfamide is currently in two Phase 3 trials, both of which are fully recruited: one in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS) (the TH-CR-406 trial), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with locally advanced unresectable or metastatic pancreatic cancer (the MAESTRO trial). Top-line data for both trials are expected around the end of 2015. Both Phase 3 trials are being conducted under Special Protocol Assessment (SPA) agreements with the FDA. The FDA and the European Commission have granted evofosfamide Orphan Drug designation for the treatment of STS and pancreatic cancer. The FDA has also granted Fast Track designation for evofosfamide for both STS and pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 trial designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical trials of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany, which includes an option for Threshold to co-commercialize in the U.S.

MabVax Therapeutics Completes Manufacturing of HuMab 5B1 for Upcoming Phase I Clinical Trials

On November 3, 2015 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage oncology drug development company, reported it has completed manufacturing of the bulk clinical-quality drug substance of HuMab 5B1 in preparation for the planned initiation of two Phase I clinical trials with this antibody in early 2016 (Press release, MabVax, NOV 3, 2015, View Source [SID:1234507911]). The bulk clinical material was manufactured under Good Manufacturing Practices (GMP), has cleared all testing and has been released to be packaged into finished product.

Paul Maffuid, Ph.D., Vice President of Development and Operations of MabVax, said, "We are pleased to have completed the manufacture of the first lot of GMP bulk drug substance which is a tribute to our staff and collaborators who aided in this effort. Production of finished drug product and the information generated during this campaign are essential components of our two Investigation New Drug (IND) submissions planned for later this year."

The first Phase I trial will evaluate the safety and utility of HuMab 5B1 as a therapeutic in subjects with metastatic pancreatic cancer as a single agent or in combination with the current standard-of-care chemotherapy regimen. The second Phase I trial will be aimed at demonstrating the utility of 89Zr-HuMab 5B1, a radiolabeled HuMab 5B1 antibody, as a next-generation PET imaging agent for the identification, imaging and monitoring of pancreatic cancer.

"We believe the safety and targeting specificity data generated in the early portions of these two Phase I trials will validate the utility of the HuMab 5B1 antibody in this devastating disease," said MabVax’s President and Chief Executive Officer David Hansen. "We are excited about the potential applicability of our dual-product development approach in other cancers with HuMab 5B1, as well as with follow-on antibodies under development at MabVax."

About HuMab 5B:

In preclinical research MabVax’s HuMab 5B1 antibody has demonstrated high specificity, affinity and lack of cross-reactivity with closely related antigens. The antibody has also shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancer. When combined with a radio-label as a novel PET imaging agent, 89Zr-HuMab 5B1 has demonstrated high image resolution of tumors in established xenograft animal models, making it attractive as a companion diagnostic for the therapeutic product.