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.

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"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.

On January 9, 2017 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a leader in the discovery and development of engineered cell-based therapies, reported that the U.S. Patent and Trade Office (USPTO) has decided to uphold Celyad’s U.S. Patent No. 9,181,527, relating to allogeneic human primary T-cells that are engineered to be TCR-deficient and express a CAR (Press release, Celyad, JAN 9, 2017, View Source [SID1234517409]).

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"We are pleased with the outcome of this re-examination of our patent related to the production of allogeneic TCR-deficient CAR-T cells. This marks the third decision by the USPTO to uphold this patent, which thus remains valid and enforceable, and provides for continued intellectual property protection for this valuable asset", said Philippe Dechamps, Chief Legal Officer of Celyad.

"Allogeneic CAR T-cells are a promising avenue to broaden the scope of application of cell based immunotherapy", said Georges Rawadi, VP Business Development and IP of Celyad. "We look forward to the further development of our own allogeneic programs and also continue to offer other parties access to this important patent to advance the field more broadly."

Celyad’s U.S. patent (No. 9,181,527), and more precisely claim 1 of the said patent, was challenged by an anonymous third party through an Ex Parte Re-examination procedure. The request for Ex Parte re-examination was filed on February 10th, 2016 and an order granting Ex Parte Re-examination of claim 1 was issued by the USPTO on March 24th, 2016. The final decision of this Ex Parte procedure that was issued on January 6th 2017 is not subject to appeal and upholds the validity of the patent.

Therefore, Celyad’s U.S. patent (No. 9,181,527), confirms continued coverage of CAR-expressing human T-cells, according to Claim 1, modified to reduce or eliminate T-cell receptor expression or function.

On January 9, 2017 ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage drug development company advancing targeted therapeutics for the treatment of patients with cancer, reported it has changed its corporate name to Sierra Oncology, Inc. and that its shares will trade on the NASDAQ under the symbol ‘SRRA’, effective on January 10th (Press release, ProNAi Therapeutics, JAN 9, 2017, View Source [SID1234517352]). The company’s new name reflects its evolution into an oncology focused company advancing an emerging pipeline of promising therapies that target the DNA Damage Response (DDR) network.

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"We believe there is a significant opportunity for therapeutics that target the DDR network to have broad potential in the treatment of cancer, and that by successfully advancing our new drug candidates in this field we may generate substantial long-term value for our company," said Dr. Nick Glover, President and CEO of Sierra Oncology.

"Our new name, Sierra Oncology, reflects our focus on this approach and the commitment of our management team to charting innovative paths for developing novel therapeutics against cancer."

Dr. Glover will be presenting an update on Sierra Oncology at the BIOTECH Showcase being held in San Francisco on January 11th. The presentation, entitled ‘Beyond PARP – Next Generation DDR Therapeutics", is scheduled for 8:00 am (PST) on Wednesday, January 11th. A live audio webcast and archive of the presentation will be accessible through the Sierra Oncology website at www.sierraoncology.com.

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.

On January 8, 2017 Ipsen (Euronext: IPN; ADR: IPSEY) reported that it has entered into a definitive agreement to acquire global oncology assets from Merrimack Pharmaceuticals (NASDAQ: MACK), including its key marketed product ONIVYDE (irinotecan liposome injection) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, in combination with fluorouracil and leucovorin (Press release, Ipsen, JAN 8, 2017, View Source [SID1234517358]). Under the terms of the agreement, Ipsen will gain exclusive commercialization rights for the current and potential future ONIVYDE indications in the U.S., as well as the current licensing agreements with Shire for commercialization rights ex-U.S. and PharmaEngine for Taiwan. The transaction also includes Merrimack’s commercial and manufacturing infrastructure, and generic doxorubicin HCl liposome injection.

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The transaction represents a unique opportunity and a strong strategic fit for Ipsen. ONIVYDE is a clinically differentiated and FDA-approved product for patients with high unmet medical needs. The transaction secures a marketed, wholly-owned asset with current U.S. revenues and significant revenue growth projections, based on solid clinical data and potential approvals in additional indications already in clinical development. Furthermore, there are significant commercial synergies to be realized by integrating the ONIVYDE franchise with the existing Ipsen U.S. oncology commercial infrastructure, which has strong expertise and a proven track record with Somatuline. As a result, this transaction strengthens Ipsen’s Oncology franchise and accelerates both its near- and long-term growth trajectory and profitability.

David Meek, CEO of Ipsen, commented, "The acquisition of ONIVYDE represents a compelling strategic opportunity to further strengthen Ipsen’s oncology portfolio while leveraging our U.S. infrastructure and creating meaningful potential incremental growth and profitability. Pancreatic cancer is now the third leading cause of cancer-related deaths. It is an area that has had many drug failures and very few FDA approvals over the past two decades. For the tens of thousands of patients living with pancreatic cancer in the U.S. who have received prior treatment with gemcitabine, ONIVYDE represents an important, differentiated innovation, given its proven overall survival benefit in an area of high unmet medical need with few approved therapies."

"ONIVYDE is a landmark, recently approved therapeutic option for metastatic pancreatic cancer. Since the launch in the fourth quarter of 2015, many patients have already benefitted from ONIVYDE." said Cynthia Schwalm, Executive Vice President, North America Commercial Operations, Ipsen. "Based on our track record of successfully bringing oncology products to patients, we are confident in our ability to leverage our operational and clinical development capabilities, and experienced commercial and medical affairs teams to ensure eligible patients have access to ONIVYDE in the U.S."

Ipsen will be responsible for advancing the ongoing ONIVYDE clinical development program, which includes a Phase 2 trial in first-line previously untreated metastatic pancreatic cancer, a Phase 2/3 trial in relapsed small-cell lung cancer, and a Phase 1 pilot trial in breast cancer.

Under the terms of the agreement, Ipsen will pay $575 million cash at closing plus up to $450 million upon the approval of potential additional indications for ONIVYDE in the U.S. The transaction will be fully financed by Ipsen’s existing cash and lines of credit. The deal should be dilutive in 2017 and accretive from 2018 onwards both in operating margin and EPS. The transaction, which is subject to customary closing conditions, including governmental regulatory clearances, and a vote by Merrimack shareholders, is expected to close by the end of the first quarter of 2017.

Ipsen was advised on this transaction by MTS Health Partners, LP and Dechert LLP.

About Pancreatic Cancer

Pancreatic cancer is a rare and deadly disease with approximately 338,000 new patients diagnosed globally each year, approximately 50,000 of which are in the United States2. More than half are diagnosed with metastatic disease who have an overall 5-year survival rate of two percent2, and often rapidly progress during or shortly after receiving chemotherapy3. Pancreatic cancer is the 3rd leading cause of cancer-related death in the United States surpassing breast cancer.2 It is expected to become the 2nd leading cause of cancer-related death in the US by the year 2030, surpassing colorectal cancer.2

About ONIVYDE

ONIVYDE is a unique encapsulation formulation of irinotecan in a long-circulating liposomal form designed to increase the length of tumor exposure to irinotecan and its active metabolite SN-38.

In the pivotal Phase 3 NAPOLI-1 study, ONIVYDE with fluorouracil and folinic acid demonstrated a statistically significant improvement of overall survival in adult patients with metastatic adenocarcinoma of the pancreas who have progressed following gemcitabine-based therapy3. Gemcitabine, both as monotherapy as well as in combination, is commonly used in the first-line treatment of locally advanced and/or metastatic pancreatic adenocarcinoma, as well as in the adjuvant (treatment after surgery) and neo-adjuvant (treatment before surgery) settings4.

Ipsen will market the product in the United States where ONIVYDE received US Food and Drug Administration (FDA) approval in October 2015 in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas who have progressed following treatment with gemcitabine-based therapy.

Shire is responsible for the development and commercialization of ONIVYDE outside of the United States and Taiwan under an exclusive licensing agreement with Merrimack Pharmaceuticals, Inc. In October 2016, the European Commission (EC) granted Marketing Authorization of ONIVYDE for the treatment of metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil (5-FU) and leucovorin (LV), in adult patients who have progressed following gemcitabine-based therapy.

The ONIVYDE product license was granted to PharmaEngine in March 2016 for commercialization rights in Taiwan.

Licenses outside the U.S. will be transferred to Ipsen.

About Generic Doxorubicin HCl Liposome Injection

Generic doxorubicin HCl Liposome Injection is currently being evaluated by the U.S. Food and Drug Administration (FDA) for the potential treatment of ovarian cancer, multiple myeloma and Kaposi’s sarcoma. Teva retains the worldwide commercial rights for this product, and Ipsen will be eligible to receive milestones and shared profits from potential sales.