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PTC Therapeutics Provides Corporate Update and Outlines 2017 Strategic Priorities to Maximize the Global Value of Translarna™ and Advance its Innovative Pipeline

On January 9, 2017 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update, which will be detailed as part of the company presentation at the 35th Annual J.P. Morgan Healthcare Conference on Wednesday, January 11th at 7:30 am PT (Press release, PTC Therapeutics, JAN 9, 2017, View Source [SID1234517388]). Stuart W. Peltz, Ph.D., PTC’s Chief Executive Officer, will present the company’s 2017 strategic priorities, preliminary 2016 financial results and 2017 financial guidance. The presentation will be webcast live and available with the related slide deck on the Events and Presentations page under the investors section of PTC Therapeutics’ website at www.ptcbio.com.

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Commercial Highlights, Preliminary 2016 Unaudited Financial Results, and 2017 Guidance

PTC expects to report Translarna (ataluren) net sales for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) of approximately $81 million for 2016, an increase of 140% over the prior year and achieving the upper-end of guidance. This strong performance reflects rapid uptake, sustainable pricing, and high ( > 90%) compliance to treatment.
PTC expects to report year-end 2016 cash and cash equivalents of approximately $230 million.
For 2017, PTC expects to achieve ex-U.S. Translarna nmDMD net sales of between $105 and $125 million, assuming current exchange rates, representing continued strong growth year-over-year of its sustainable DMD business. This is driven by both increased penetration into the over 25 countries where Translarna is currently available as well as continued geographic expansion into new territories.
Non-GAAP operating expenses for 2017 are expected to be between $190 and $200 million excluding estimated non-cash stock-based compensation expense of approximately $35 million, for total operating expenses of approximately $225 to $235 million.
PTC expects to finish 2017 with approximately $160 million of cash and cash equivalents.
Clinical and Regulatory Highlights

Following multiple interactions with U.S. FDA officials and PTC’s advisors, PTC plans to file the Translarna New Drug Application (NDA) for nmDMD over protest with the U.S. FDA in the first quarter of 2017. Feedback indicated this process, rather than continued appeal, is the best path forward for the current Translarna NDA to receive a full and fair review. Filing over protest is a procedural path permitted by U.S. FDA regulations that allows a company to have its NDA filed and reviewed when there is a disagreement with regulators over the acceptability of the NDA submission. PTC plans to supplement the current NDA with additional efficacy analyses utilized by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in their recent renewal recommendation.
The EMA’s CHMP recommended the renewal of the conditional marketing authorization for Translarna (ataluren) for the treatment of nmDMD based on a continued positive benefit-risk assessment. As a specific obligation of the renewal, PTC will conduct an additional trial of Translarna in nmDMD.
Top-line results of ACT CF are anticipated late in the first quarter of 2017. ACT CF is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled trial that is evaluating the absolute change in percent predicted forced expiratory volume in one second (FEV1) in patients with nonsense mutation cystic fibrosis (nmCF).
The spinal muscular atrophy (SMA) program, a joint collaboration with Roche and the SMA Foundation, is expected to advance into two pivotal studies in 2017. SUNFISH and FIREFISH are both two part studies in childhood onset (Type 2/3) and infant onset (Type 1) SMA patients, respectively. Both studies are enrolling the initial dose escalation part of the study which will then transition to the pivotal part of the study evaluating efficacy. Commencement of the pivotal portion of either study will trigger a $20 million milestone payment to PTC from Roche. RG7916 was recently granted orphan-drug designation by the U.S. FDA.
Pipeline Highlights:

Phase 2 proof-of-concept studies of Translarna in additional rare disease indications, including aniridia, MPS I, and Dravet/CDKL5, continue to progress. Proof-of-concept from these studies would further validate Translarna’s potential as a precision medicine for a number of rare genetic disorders caused by a nonsense mutation.
Clinical development of PTC596 is expected to progress into additional clinical studies in 2017. PTC596 is a novel, oral investigational drug that reduces the levels of BMI1, a protein required for cancer stem cell survival. An ongoing Phase 1 dose escalating study confirms that PTC596 is generally well tolerated at doses that achieved or exceed plasma concentrations in preclinical models.
PTC’s genetic disorders research organization is actively advancing lead optimization programs from its splicing platform focused on Huntington’s disease and Familial Dysautonomia.

Infinity Provides 2017 Goals and Financial Guidance

On January 9, 2017 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported anticipated milestones for IPI-549, a potentially first-in-class immuno-oncology product candidate that selectively inhibits PI3K-gamma, and provided financial guidance for 2017 (Press release, Infinity Pharmaceuticals, JAN 9, 2017, View Source;p=RssLanding&cat=news&id=2234986 [SID1234517387]). During the year, Infinity expects to make substantial progress with the Phase 1 clinical study of IPI-549, which is designed to evaluate IPI-549 both as a monotherapy and in combination with Opdivo, a PD-1 immune checkpoint inhibitor. In 2017, the company also plans to report updated Phase 1 clinical data from the monotherapy dose-escalation as well as initial clinical data from the combination dose-escalation phase. Additionally, Infinity expects to complete the monotherapy and combination dose-escalation phases of the study and initiate monotherapy and combination expansion cohorts this year. The company also announced today that it has completed patient enrollment in the first dose-escalation cohort evaluating IPI-549 plus Opdivo. These updates were made in conjunction with the 35th Annual J.P. Morgan Healthcare Conference that begins today in San Francisco. Infinity’s chief executive officer, Adelene Perkins, will discuss the company’s continued execution on its corporate strategy and 2017 priorities as part of a live presentation on Thursday, January 12, at 10:30 a.m. PT (1:30 p.m. ET). The presentation will be webcast on Infinity’s website, www.infi.com.

"We enter 2017 intensely focused on advancing IPI-549 and, having already fully enrolled the first dose-escalation cohort evaluating IPI-549 plus Opdivo, we are off to a strong start to the year. Preclinical data in two recent Nature publications provide a compelling rationale for advancing IPI-549 and show that IPI-549 in combination with immune checkpoint inhibitors may overcome resistance to checkpoint blockade," stated Adelene Perkins, Infinity’s chief executive officer. "IPI-549 represents a unique approach to targeting tumors through its effects on the tumor microenvironment, and we look forward to presenting updated monotherapy and initial combination data from our Phase 1 study this year."

The tumor microenvironment, or TME, refers to the non-cancerous cells present in the tumor. Cells within the TME, including immune-suppressive myeloid cells, can provide growth signals to tumor cells, as well as signals that inhibit an anti-tumor immune response. The presence of the supportive TME is believed to be one reason why some cancer therapies do not provide durable or effective results. Targeting the immune-suppressive myeloid cells represents an emerging approach within the field of cancer immunotherapy, and inhibition of PI3K-gamma represents a novel approach to targeting the immune-suppressive microenvironment. Preclinical data recently published in Nature suggest that IPI-549 may enhance the effects of checkpoint inhibitors and may also reverse tumor resistance to checkpoint inhibitors by targeting immune cells and altering the immune-suppressive microenvironment, promoting an anti-tumor immune response.1,2

Today Infinity also announced that on Friday, January 20, 2017, preclinical and initial clinical data from the Phase 1 study of IPI-549 will be presented at the Keystone Symposia Conference, ‘PI3K Pathways in Immunology, Growth Disorders and Cancer.’ Jeffery Kutok, M.D., Ph.D., vice president of biology and translational science at Infinity, will give the presentation, entitled "The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical tumor models."

"With IPI-549, we have a tremendous opportunity to potentially further improve response rates and survival for patients by overcoming resistance to immune checkpoint inhibitors," said Lawrence Bloch, M.D., J.D., president of Infinity. "We have an experienced and right-sized team that is well-resourced and fully focused on maximizing the value of IPI-549, with a cash runway into the first quarter of 2019."

2017 Program Goals for IPI-549
Infinity expects to achieve the following duvelisib milestones in 2017:

Present preclinical and clinical data from Phase 1 study at the upcoming PI3K Keystone Symposia Conference in January 2017
Report Phase 1 data from the monotherapy dose-escalation phase as well as the IPI-549 plus Opdivo dose-escalation phase in 2017
Complete the dose-escalation phase evaluating IPI-549 monotherapy in the first half of 2017
Begin enrolling patients with advanced solid tumors in the monotherapy expansion cohort during the second half of 2017
Complete the dose-escalation combination phase evaluating IPI-549 plus Opdivo in the second half of 2017
Begin enrolling patients with non-small cell lung cancer (NSCLC), melanoma and squamous cell carcinoma of the head and neck (SCCHN) in combination expansion cohorts evaluating IPI-549 plus Opdivo in the second half of 2017
Cash and Investments Outlook
Infinity ended 2016 with approximately $92.1 million in cash and investments (unaudited) and plans to report its fourth quarter and full-year 2016 financial results in March. The company is providing the following financial guidance today:

Net loss: Infinity expects net loss for 2017 to range from $40 million to $50 million.
Cash and Investments: Infinity expects to end 2017 with a year-end cash and investments balance ranging from $40 million to $50 million.
Based on its current operational plans, Infinity expects that its existing cash, cash equivalents and available-for-sale securities at December 31, 2016, will be adequate to satisfy the company’s capital needs into the first quarter of 2019.
The company’s financial outlook excludes additional funding or business development activities and includes expenses related to duvelisib beyond November 1, 2016, capped at $4.5 million, as well as costs related to Infinity’s 2016 restructuring. Additionally, Infinity’s updated cash runway expectation assumes receiving a $6.0 million milestone payment from Verastem for positive DUO study results.

IPI-549 Phase 1 Study Details
The ongoing Phase 1 clinical study of IPI-549 is designed to explore the activity, safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in patients with advanced solid tumors. The study includes monotherapy and combination dose-escalation phases, in addition to expansion cohorts, and is expected to enroll approximately 175 patients.

The IPI-549 monotherapy dose-escalation phase is expected to be completed in the first half of 2017, and the monotherapy expansion phase in patients with advanced solid tumors is anticipated to begin in the second half of the year. Once the dose-escalation phase evaluating IPI-549 plus Opdivo is completed, an expansion phase is planned to evaluate the combination in patients with select solid tumors, including NSCLC, melanoma and SCCHN. Patients enrolled in expansion cohorts evaluating IPI-549 plus Opdivo represent a difficult-to-treat population, as they must have demonstrated de novo or acquired resistance to an immediately prior therapy of an inhibitor of PD-1 or PD-L1.

Although there has been great progress in the treatment of cancer, there remains a need for additional treatment options. NSCLC, melanoma and SCCHN, which will comprise three of the expansion cohorts in this Phase 1 study, account for more than 17 percent of all new cancer cases in the U.S.3,4

About IPI-549
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical tumor models. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors. A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing.5

IPI-549 is an investigational compound, and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

Celgene Corporation Announces Preliminary 2016 Unaudited Results and 2017 Financial Guidance

On January 9, 2017 Celgene Corporation (NASDAQ: CELG) reported a business update as well as its preliminary 2016 unaudited results and financial guidance for 2017 at the 35 th Annual J.P. Morgan Healthcare Conference (Press release, Celgene, JAN 9, 2017, View Source [SID1234517385]). In 2017, total revenue is expected to be approximately $13.0 billion to $13.4 billion, an 18 percent increase year-over-year, based on the mid-point of the range. The negative impact of foreign exchange on total revenue is expected to be approximately $170 million in 2017. For the full-year 2017, REVLIMID net sales are expected to be in the range of $8.0 billion to $8.3 billion.

Based on U.S. Generally Accepted Accounting Principles (GAAP), diluted earnings per share (EPS) for the full-year 2017 is expected to be in the range of $5.85 to $6.21, excluding the impact of any strategic transactions, impairments and loss contingencies that have not yet occurred. For the full-year 2017, adjusted diluted EPS is expected to be in the range of $7.10 to $7.25, a 21 percent increase year-overyear, based on the mid-point of the range.

"In 2016, we made exceptional progress strengthening and growing our franchises while accelerating and adding to our robust pipeline; our significant business momentum supports raising our 2017 guidance," said Mark J. Alles, Chief Executive Officer of Celgene. "We are entering a pivotal two-year period with multiple catalysts increasing our confidence in our ability to achieve or exceed our 2020 targets and sustain our growth from 2020 to 2030."

Preliminary 2016 Financial Results Year-Over-Year (Unaudited)
Total net product sales are expected to be approximately $11,187 million, up 22 percent year-overyear.
REVLIMID: $6,976 million, 20 percent year-over-year increase
POMALYST/IMNOVID: $1,311 million, 33 percent year-over-year increase
OTEZLA: $1,017 million, 116 percent year-over-year increase
ABRAXANE: $973 million, 1 percent year-over-year increase 2

GAAP operating margin is expected to be approximately 28 percent, an increase from 24 percent in the prior year, primarily due to increased product sales. Full-year 2016 GAAP diluted EPS is expected to be in the range of $2.43 to $2.51, a 27 percent year-over-year increase.

Adjusted operating margin is expected to be approximately 55 percent for the full year, an increase of 290 basis points (bps) year-over-year. Adjusted diluted EPS is expected to be approximately $5.94, a 26 percent year-over-year increase.
Certain activities involved in determining the audited results for the fiscal year ended December 31, 2016 are in-process and could result in the final reported audited results being different from the unaudited results noted in this press release. Additionally, please see the attached Use of Non-GAAP Financial Measures and Reconciliation of Estimated/Projected GAAP to Adjusted (Non-GAAP) Measures for further information relevant to the interpretation of adjusted financial measures and reconciliations of these adjusted financial measures to the most comparable GAAP measures, respectively, for each of 2016 and 2017.
Celgene Expects Strong Product Sales and Earnings Growth in 2017 Year-over-Year Change* Total Revenue Approximately $13.0B to $13.4B 18% REVLIMID Net Sales Approximately $8.0B to $8.3B 17% POMALYST/ IMNOVID Net Sales Approximately $1.6B 22% OTEZLA Net Sales Approximately $1.5B to $1.7B 57% ABRAXANE Net Sales Approximately $1.0B 3% GAAP diluted EPS $5.85 to $6.21 N/M** Adjusted diluted EPS $7.10 to $7.25 21% GAAP operating margin Approximately 45.5% N/M** Adjusted operating margin 56.4% +150bps Weighted average diluted shares ~815M +12M
*Year-over-year percentage change based on mid-point in range.
**Not meaningful as the 2017 measures exclude the impact of any strategic transactions, impairments and loss contingencies that have not yet occurred.

Reaffirming Expected 2020 Long-term financial Targets
2020 Total Revenue to exceed $21 billion
Adjusted Diluted EPS to exceed $13.00

2017 Expected Operational Milestones
Hematology/Oncology
Regulatory Submissions/Decisions
Decision by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) 3 on REVLIMID as maintenance treatment for patients with multiple myeloma following autologous stem cell transplant
Submission of a supplemental New Drug Authorization (sNDA) to the U.S. FDA for REVLIMID in combination with bortezomib and dexamethasone (RVd) in patients with newly diagnosed multiple myeloma (NDMM)
Approval by the U.S. FDA for enasidenib (AG-221) for the treatment of patients with relapsed and/or refractory acute myeloid leukemia (AML) with isocitrate dehydrogenase-2 (IDH2) mutation

Clinical Data
Data from the phase III RELEVANCE trial with REVLIMID in combination with rituximab in patients with newly diagnosed follicular lymphoma (FL)
Data from the phase III AUGMENT trial with REVLIMID in combination with rituximab in patients with relapsed and/or refractory FL
Data from the phase III apact (PANC-003) trial with ABRAXANE as adjuvant therapy in patients with surgically resected pancreatic cancer
Data from the phase IV abound.70+ trial with ABRAXANE in combination with carboplatin as a first-line treatment in patients with advanced non-small cell lung cancer (NSCLC)
Data from the phase II abound.PS2 trial with ABRAXANE in combination with carboplatin as a first-line treatment in patients with advanced NSCLC and an Eastern Cooperative Group (ECOG) performance status of 2 (PS2)
Data from the phase II abound.2L+ trial with ABRAXANE alone or in combination with CC-486 or durvalumab as a second or third-line treatment in patients with advanced non-small cell lung cancer
Data from the phase II trial with CC-486 in combination with fulvestrant in patients with ER+, HER2 breast cancer
Data from phase I/II trials with CC-122 and CC-220 in patients with relapsed and/or refractory multiple myeloma
Data from the phase I/II FUSION trial evaluating durvalumab as a single agent or in combination with novel agents in patients with relapsed and/or refractory multiple myeloma (RRMM), myelodysplastic syndromes and AML in collaboration with AstraZeneca, plc.
Data from the phase II YOSEMITE trial with demcizumab in combination with ABRAXANE in patients with first-line metastatic pancreatic cancer in collaboration with OncoMed Pharmaceuticals, Inc.
Data from the phase II DENALI trial with demcizumab in patients with first-line advanced stage NSCLC in collaboration with OncoMed Pharmaceuticals, Inc.
Trial Enrollment
Complete enrollment in the phase III OPTIMISMM trial with POMALYST/IMNOVID in second-line RRMM
Complete enrollment in the phase III ROBUST trial with REVLIMID in newly diagnosed diffuse large B-cell lymphoma (DLBCL)
Complete enrollment in the phase III QUAZAR trial with CC-486 in post-induction AML maintenance
Complete enrollment in the phase III MEDALIST trial with luspatercept in patients with low and INT-1 myelodysplastic syndrome with ring sideroblasts who require red blood cell (RBC) transfusions
Complete enrollment in the phase III BELIEVE trial with luspatercept in patients with beta- 4 thalassemia who have regular RBC transfusions
Trial Initiations
Initiate enrollment in a phase III trial with CC-122 in relapsed and/or refractory non-Hodgkin lymphoma (NHL)
Initiate enrollment in a pivotal program with marizomib in glioblastoma
Initiate enrollment in a phase II trial with luspatercept in myelofibrosis in collaboration with Acceleron Pharma, Inc.
Initiate enrollment in a phase II trial with bb2121, a B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy, in RRMM in collaboration with bluebird bio, Inc.
Initiate enrollment in a pivotal program with JCAR017 in relapsed and/or refractory non-Hodgkin lymphoma in collaboration with Juno Therapeutics, Inc.

Inflammation and Immunology (I&I)
Regulatory Submissions/Decisions
Submission of an sNDA for OTEZLA once-daily formulation
Submission of an NDA for ozanimod in patients with multiple sclerosis

Clinical Data
Data from the phase III SUNBEAM and RADIANCE trials with ozanimod in multiple sclerosis
Data from the phase II STEPSTONE trial with ozanimod in Crohn’s disease
Data from a phase II trial with GED-0301 in ulcerative colitis
Data from a phase II trial with OTEZLA in ulcerative colitis

Trial Enrollment
Complete enrollment in the phase III TRUE NORTH trial with ozanimod in ulcerative colitis
Complete enrollment in the phase III REVOLVE trial (CD-002) with GED-0301 in Crohn’s disease
Complete enrollment in the phase III RELIEF trial with OTEZLA in Behçet’s disease
Complete enrollment in a phase II trial (UC-001) with OTEZLA in ulcerative colitis
Complete enrollment in a pediatric phase II trial (PPSO-001) with OTEZLA in psoriasis

Trial Initiations
Initiate enrollment in a phase III trial with RPC-4046 in eosinophilic esophagitis Initiate enrollment in a phase III trial with OTEZLA in scalp psoriasis
Initiate enrollment in a phase III trial with OTEZLA in ankylosing spondylitis
Initiate enrollment in a phase IIb trial with CC-220 in systemic lupus erythematosus
Initiate enrollment in a phase IIa trial with CC-90001 in idiopathic pulmonary fibrosis

Research and Early Development
File at least 8 Investigational New Drug (IND) or Clinical Trial Applications (CTA)
Submission of an IND for a new CELMoD compound in patients with multiple myeloma
Submission of an IND for EM901, a T-cell bi-specific antibody targeting BCMA in patients with multiple myeloma

Agios Announces Key Upcoming Milestones to Support Evolution to a Commercial Stage Biopharmaceutical Company in 2017

On January 9, 2017 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic diseases, reported key 2017 milestones in conjunction with its presentation at the 35th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 9, 2017, View Source;p=RssLanding&cat=news&id=2234926 [SID1234517384]). The presentation will outline important milestones as Agios evolves into a commercial stage company, including potential launches for enasidenib and AG-120 in R/R AML, pivotal development for its second wholly owned asset, AG-348 in pyruvate kinase (PK) deficiency, and an investigational new drug (IND) application submission for the company’s next development candidate, focused on MTAP deleted cancers. The company will webcast its presentation on Monday, January 9, 2017 at 10:00 a.m. PT (1:00 p.m. ET) at www.agios.com.

"This is the year Agios will evolve into a commercial-stage organization with the anticipated launch of enasidenib for patients with R/R AML, followed by the NDA submission of AG-120 and AG-348 preparing to enter a pivotal trial in PK deficiency," said David Schenkein, M.D., chief executive officer of Agios. "We believe these milestones will enable us to achieve our vision of delivering important medicines with the potential to transform patients’ lives. Additionally, our robust research engine continues to be highly productive with an IND submission for the company’s sixth development candidate in eight years anticipated by the end of 2017."

The company expects to achieve the following key milestones by the end of 2017:

Potential approval of enasidenib in the United States for IDH2m positive R/R AML in collaboration with Celgene.
Submit a new drug application (NDA) to the U.S. FDA for AG-120 by the end of 2017. AG-120 is a wholly owned, first-in-class, oral, selective, potent inhibitor of IDH1m, in IDH1m positive R/R AML.
Initiate a global, registration-enabling Phase 3 study combining AG-120 and VIDAZA in frontline AML patients with an IDH1 mutation ineligible for intensive chemotherapy in the first half of 2017.
Finalize design and operational activities for a global pivotal trial of AG-348 to initiate in the first half of 2018. AG-348 is a wholly owned, first-in-class, oral activator of both wild-type (normal) and mutated pyruvate kinase-R (PKR) enzymes, in PK deficiency.
File an IND application for the MTAP pathway development candidate by the end of 2017.
The company also provided an update on the following 2016 milestones achieved in December:

Supported Celgene’s submission of an NDA for enasidenib in IDH2m positive R/R AML.
Initiated a global, registration-enabling randomized Phase 3 trial for AG-120 in IDH1m positive cholangiocarcinoma. The FDA also granted AG-120 Fast Track Designation for the treatment of patients with previously treated, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation.
Selected a development candidate focused on the MTAP pathway to enter IND-enabling studies.
2016 Year-End Cash and Guidance

Agios ended 2016 with approximately $574 million of cash, cash equivalents and marketable securities. Based on its current operating plans, the company expects that its existing cash, cash equivalents and marketable securities as of December 31, 2016, together with anticipated interest income, and anticipated expense reimbursements under its collaboration agreements with Celgene, but excluding any additional program-specific milestone payments from Celgene, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2018.

Advaxis Provides 2017 Business Outlook

On January 9, 2017 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported its 2017 business outlook to provide an overview of anticipated events and key milestones for the coming year, as well as a look back at clinical and business highlights from 2016 (Press release, Advaxis, JAN 9, 2017, View Source [SID1234517383]).

Advaxis made significant strides in its clinical development programs and expanded its pipeline with additional preclinical assets in 2016. The company’s lead product candidate, axalimogene filolisbac, received Fast Track designation and a Special Protocol Assessment (SPA) for the global Phase 3 AIM2CERV study, a randomized study of axalimogene filolisbac following chemoradiation in patients with high-risk, locally advanced cervical cancer (HRLACC). Also in 2016, axalimogene filolisbac was classified as an advanced therapy medicinal product (ATMP) for the treatment of cervical cancer by the European Medicines Agency’s (EMA) Committee for Advanced Therapies (CAT). Late in 2016, the company initiated AIM2CERV and announced positive, final data from the GOG-0265 Phase 2 trial that supports pursuing a second global Phase 3 study in a metastatic recurrent cervical cancer. Also in 2016, Advaxis entered into a collaboration with Amgen Inc. (Amgen) for the global development and commercialization of Advaxis’ preclinical neoantigen technology, ADXS-NEO, to create a personalized approach to cancer treatment.

In 2016, Advaxis expanded its capabilities and added significant resources to support execution of two global registrational clinical trials and future commercialization of its immuno-oncology products. The company added close to $100 million in capital from proceeds from the Amgen collaboration, a direct placement and a state grant. Advaxis expanded its management team in 2016 with the appointment of Chris Duke as Chief Operating Officer, and added approximately 30 more employees in key areas, as the company grew its headcount to 80 over the course of the year. In September, the company completed the buildout of its clinical manufacturing facility to produce clinical trial supplies and expanded its research laboratory facility. Also, the company began construction of its commercial manufacturing facility, all at its Princeton headquarters.

2017 OPERATIONAL MILESTONES

Advaxis anticipates the following development milestones in 2017:

Clinical Operations

Axalimogene Filolisbac

Present a detailed data analysis of the completed Phase 2 GOG-0265 trial, which was conducted by the GOG Foundation, Inc. (GOG, now part of NRG Oncology), evaluating patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), at a medical meeting in the first half of 2017. Top-line data released in 2016 showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.
Attend an end-of-Phase-2 meeting with respect to PRmCC with the U.S. Food and Drug Administration (FDA) to discuss the results of GOG-0265.
Submit a marketing authorization application to the EMA for approval of axalimogene filolisbac to treat patients with metastatic cervical cancer in the second half of 2017.
Open approximately 150 clinical sites for the global, 450-patient Phase 3 AIM2CERV trial in patients with HRLACC, with a trial enrollment update to be issued at a medical meeting in the first half of 2017. There are 10 active trial sites in the United States as of this week.
Initiate a second global, registrational Phase 3 study in patients with metastatic cervical cancer in the second half of 2017.
Present updated clinical data from the Phase 1/2 combination trial with AstraZeneca’s investigational anti-PD-L1 inhibitor, durvalumab, in patients with recurrent, persistent or metastatic cervical cancer or HPV+ squamous cell cancer of the head and neck (HNSCC) at a medical meeting in the second half of 2017.
Present additional data from the Phase 2 BrUOG trial in high-risk, locally advanced anal cancer, conducted in collaboration with Brown University’s Oncology Research Group, at a medical meeting in the first half of 2017.
Present additional data from the Phase 2 window of opportunity trial in HPV-positive head and neck cancers at a medical meeting in the first half of 2017.
With full enrollment achieved in Stage 1 of the FAWCETT Phase 2 trial in patients with persistent or recurrent metastatic anal cancer, the company plans to present a preliminary trial update at a medical meeting in the second half of 2017.
ADXS-PSA

Complete initial dosing of Part B of the Phase 1/2 trial evaluating ADXS-PSA in combination with KEYTRUDA (pembrolizumab) in advanced, metastatic castration-resistant prostate cancer (mCRPC) and present preliminary data at a medical meeting in 2017.
Initiate and complete enrollment of the expansion cohort by year-end 2017.
ADXS-HER2

Initiate a study in pediatric osteosarcoma in collaboration with the Children’s Oncology Group in 2017.
Expanding Pipeline

ADXS-NEO Collaboration with Amgen

Submit an Investigational New Drug (IND) application to the FDA in early 2017.
Initiate the first-in-human ADXS-NEO clinical trial.
Accelerate the discovery of personalized cancer immunotherapies derived from neoantigens as part of the TESLA (Tumor neoantigEn SeLection Alliance) with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute.
ADXS-HOT

Prepare and file an IND with the FDA for ADXS-HOT constructs that target tumor driver genes, so-called hotspot mutations or public mutations, found in various cancer types in the second half of 2017.
Enhanced Manufacturing and Research Capabilities

Increase capacity to include in-house clinical and commercial manufacturing capabilities, initially to manufacture clinical supplies for the ADXS-NEO program in 2017.
Reduce lead times and improve overall supply chain by operationalizing several technology transfers with its partners and by installing new innovative technologies.
Corporate Development

Pursue research, clinical and commercial partnerships to optimize the cancer immunotherapy portfolio, including to enable development of lead asset, axalimogene filolisbac, in combination with other novel cancer therapies and to support its registration and potential commercialization in the EU.
Explore the application of detoxified Listeriolysin O (dtLLO) technology and optimize the research and development as an adjuvant molecule in the development of vaccines.
2016 REVIEW

Advaxis achieved several regulatory, clinical, business and operational milestones in 2016:

Clinical Milestones

Axalimogene Filolisbac

June: Presented preliminary data at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) from stage 1 of the Phase 2 GOG-0265 clinical study showing a 6-month survival rate of 38.5 percent in 26 patients, which exceeds prior historical GOG trials in this patient population. Of particular note, a patient from this stage experienced a complete response following three doses which remains ongoing.
June: Dosed the first patient in the first stage of the Phase 2 FAWCETT trial in patients with persistent or recurrent metastatic anal cancer.
July: Reached an agreement with the FDA under the SPA process for the Phase 3 AIM2CERV trial.
July: Received classification as an ATMP for the treatment of cervical cancer by the EMA’s CAT and received Fast Track Designation from the FDA for high-risk, locally advanced cervical cancer.
October: Entered Phase 3 with initiation of AIM2CERV evaluating axalimogene filolisbac as an adjuvant therapy following chemotherapy and radiation.
October: Announced updated data from the Phase 2 GOG-0265 clinical study which showed a patient with recurrent cervical cancer achieved a durable complete response, as well as a 12-month overall survival rate of 38 percent across all study subjects (n=50), surpassing historical 12-month survival rates in GOG studies which have never exceeded 30 percent.
November: As presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting, a patient with cervical cancer participating in the combination trial with AstraZeneca’s durvalumab achieved a complete response, and two patients with HNSCC achieved stable disease.
April: The window of opportunity trial, as presented as American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, showed increased systemic HPV-reactive T-cell responses in patients with late-stage HPV-positive oropharyngeal cancer, allowing for the trial to advance to the second stage, being conducted at the Icahn School of Medicine at Mount Sinai.
ADXS-PSA

April: Finalized the part A dose-escalation cohort of the Phase 1/2 KEYNOTE-046 combination trial with Merck, which evaluated maximum tolerability of ADXS-PSA in patients with previously treated mCRPC.
October: Initiated the combination portion evaluating ADXS-PSA in combination with KEYTRUDA.
ADXS-HER2

May: As published in Clinical Cancer Research, in a dose-escalation study of ADXS-HER2 in canine osteosarcoma, antigen-specific T-cell responses were seen within 6 months of immunotherapy administration.
April: FDA granted Fast Track designation for ADXS-HER2 for patients with newly diagnosed, non-metastatic, surgically-resectable osteosarcoma.
Expanding Pipeline

ADXS-NEO

January: Established a five-year exclusive supply agreement with Synthetic Genomics, Inc. to manufacture the synthetic DNA used in ADXS-NEO.
August: Advaxis entered into a global collaboration with Amgen to develop and commercialize ADXS-NEO. Under the collaboration agreement, Advaxis will lead the clinical development of ADXS-NEO through proof-of-concept, retain manufacturing responsibilities, and receive development, regulatory and sales milestone payments of up to $475 million. Amgen received worldwide rights to develop and commercialize ADXS-NEO.
December: Advaxis joined the TESLA (Tumor neoantigEn SeLection Alliance) collaboration with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute, along with 30 leading academia and industry partners, to further cancer neoantigen research.
Business & Operations

Advaxis achieved the following operational milestones in 2016:

Over the course of 2016, Advaxis expanded its leadership team, deepening its clinical operations, manufacturing and business development functions:
Christopher Duke, Senior Vice President and Chief Operating Officer.
Ranya Dajani, Vice President, Corporate Development
January: Established a Scientific Advisory Board, including Antoni Ribas, M.D., Ph.D., Jedd Wolchok, M.D., Ph.D., Nancy Freitag, Ph.D., Marc Lecuit, M.D., Ph.D.
January: Added two more patents to its growing patent portfolio; European Patent No. 1804831 expands the composition of matter claims covering HER-2 tumor antigens, and U.S. Patent No. 9,226,958 expands the use of the Company’s Lm Technology beyond oncology, specifically to induce an immune response in parasitically infected patients.
February: Bradley Monk, co-primary investigator of the GOG-0265 Phase 2 study, joined Advaxis as the company’s Lead Cervical Cancer Advisor to head the development of Advaxis’ Lm Technology platform and lead the AIM2CERV program.
February: Agreement established with Especificos Stendhal SA de CV ("Stendhal") to co-develop and commercialize axalimogene filolisbac in Latin America.
February: Daniel O’Connor, president and chief executive officer of Advaxis, was appointed to the Board of Trustees of BioNJ.
April: Advaxis became the first biotechnology company to receive the Vision of Hope Award from the Sarcoma Foundation of America for its ADXS-HER2 osteosarcoma immunotherapy platform.
August: Advaxis secured $30 million in direct placement financing from healthcare institutional specialist investors.
September: Advaxis unveiled its state-of-the-art laboratory and manufacturing facility to develop immuno-oncology therapeutics in Princeton N.J. where Governor Chris Christie led the ribbon-cutting event.
October: Advaxis received $2.5M through the New Jersey Economic Development Authority’s (NJEDA) New Jersey Technology Business Tax Certificate Transfer (NOL) program.