On January 8, 2018 Incyte Corporation (NASDAQ:INCY) and Syros Pharmaceuticals, Inc. (NASDAQ:SYRS) reported that the companies have entered into a target discovery, research collaboration and option agreement. Under the agreement, Syros will use its proprietary gene control platform to identify novel therapeutic targets with a focus in myeloproliferative neoplasms (MPNs), and Incyte will receive options to obtain exclusive worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets (Press release, Incyte, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325356 [SID1234522990]). Incyte will have exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those validated targets.

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"The discovery and development of novel therapeutic approaches to treat MPNs is an important area of focus at Incyte," said Reid Huber, Ph.D., Chief Scientific Officer of Incyte. "Through this collaboration, we believe that Syros’ gene control platform will allow us to advance our understanding of the underlying biology of MPNs and potentially uncover new molecular targets for drug discovery."

"Our gene control platform has broad applicability across diseases," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "By working with Incyte, a leader in the discovery, development and commercialization of therapies for MPNs, we aim to leverage the promise of our platform to benefit patients with diseases beyond our current areas of focus. Meanwhile, we can continue advancing our own pipeline to achieve our long-term goal of building a fully integrated company with therapies that make a profound difference for patients."

Terms of the Agreement

Under the terms of the agreement, Incyte will pay Syros $10 million upfront – including $2.5 million in cash and $7.5 million in prepaid research and development (R&D) – and purchase a total of $10 million in Syros common stock at $12.61 per share.

Should Incyte exercise all of its options under the agreement, Syros could receive up to $54 million from Incyte in target selection and option exercise fees. For products resulting from the collaboration against each of the up to seven selected and validated targets, Syros could receive up to $50 million in development and regulatory milestones, as well as up to $65 million in commercial milestones. Syros would also be eligible to receive low single-digit royalties on sales of products resulting from the collaboration.

The transaction is effective immediately.

On January 8, 2018 NewLink Genetics Corporation (NASDAQ: NLNK) reported Indigo301, the name of its upcoming Phase 3 trial of indoximod plus PD-1 inhibitors for patients with advanced melanoma, and outlined 2018 business priorities to support this trial (Press release, NewLink Genetics, JAN 8, 2018, View Source [SID1234522989]). In addition, the company updated clinical and financial guidance and provided preliminary unaudited financial information for year-end 2017.

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These updates were made in conjunction with the 36th Annual JP Morgan Healthcare Conference that begins today in San Francisco. NewLink Genetics’ Chairman and Chief Executive Officer, Charles J. Link, Jr., M.D., will discuss the Company’s continued execution of its corporate strategy and 2018 priorities as part of a live presentation on Thursday, January 11, 2018, at 11:00 AM PT/2:00 PM ET. The slide presentation with updated guidance has been posted on the Company’s website and may be found here. The oral presentation will be webcast and available on the NewLink Genetics website under the Investors & Media tab under Events & Presentations.

Indigo301 is a randomized Phase 3 study of indoximod or placebo plus KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) for patients with unresectable or metastatic melanoma. The choice of PD-1 inhibitors will be at the physician’s discretion, mirroring the general clinical setting. The study will consist of a planned 624 patients enrolled at approximately 100 sites in multiple countries and will include co-primary endpoints of Progression-Free Survival (PFS) and Overall Survival (OS), with a secondary endpoint of Objective Response Rate (ORR).

"NewLink has focused its business priorities on the execution of Indigo301 for patients with advanced melanoma," said Dr. Link. "We will also initiate a randomized Phase 2 trial in collaboration with AstraZeneca for patients with metastatic pancreatic cancer, and we anticipate clinical data from additional development programs."

To expedite the enrollment of Indigo301, NewLink Genetics has expanded the planned number of trial sites both within and outside of the US and plans several clinical recruitment initiatives to engage with the oncology community with the goal to enroll the majority of patients in 2018. As a result of these clinical planning efforts, NewLink Genetics is accordingly updating its guidance for clinical trials as follows:

Clinical Guidance and Milestones

•
Enroll the majority of Indigo301 trial by the end of 2018
•
Phase 2 results for indoximod + PD-1 blockade in advanced melanoma expected in 2018
•
Phase 2 results for indoximod + gem/nab-paclitaxel in pancreatic cancer expected 1H 2018
•
Phase 2 randomized AstraZeneca collaboration in pancreatic cancer to initiate 1H 2018

Financial Guidance and Outlook

"Entering 2018, we have aligned our business and investments to drive Indigo301 and other high-potential development programs," said Jack Henneman, Executive Vice President and Chief Financial Officer for NewLink Genetics. "As we continue to progress, we remain committed to maintaining the strength of our balance sheet in support of our most promising clinical programs."

NewLink Genetics ended 2017 with approximately $158 million in cash and cash equivalents. Updated guidance for use of cash is provided in the slide presentation available on the company’s website.

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape. NewLink Genetics is currently evaluating indoximod in multiple combination studies for patients with various types of cancer including melanoma, pancreatic cancer and other malignancies.

On January 8, 2018 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported the achievement of four development milestones for IPI-549, a first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage function and increasing anti-tumor macrophage function (Press release, Infinity Pharmaceuticals, JAN 8, 2018, View Source [SID1234522986]).

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First, the Phase1/1b monotherapy expansion component of the study has been fully enrolled. Second, the combination dose escalation component of the study has been completed. Third, six disease-specific combination expansion cohorts are open to enrollment at the recommended phase 2 dose of 40mg daily of IPI-549 plus Opdivo (nivolumab) at 240 mg every two weeks in patients with non-small cell lung cancer, melanoma, triple negative breast cancer, head and neck cancer, mesothelioma, and adrenocortical carcinoma. Fourth, the company announced today the expansion of its Phase 1/1b clinical trial of IPI-549 to include a combination cohort of IPI-549 plus Opdivo that will enroll patients with high baseline levels of myeloid derived suppressor cells (MDSCs). Studies have shown that poor response to checkpoint inhibitor therapy is correlated with the presence of high baseline levels of MDSCs in cancer patients.1 2 3 In addition, preliminary translational data from Infinity’s Phase 1/1b study demonstrated an association between high baseline levels of MDSCs and clinical responses. Enriching for patients with high MDSCs could lead to improved clinical activity for patients treated with the combination of IPI-549 and anti-PD1. Infinity expects to begin enrolling this combination expansion cohort in patients with high baseline levels of MDSCs in the first quarter of 2018.

Infinity also provided financial guidance for 2018 and outlined anticipated 2018 milestones for the development of IPI-549. During the year, the company expects to make substantial progress with the Phase 1/1b clinical study of IPI-549, which is designed to evaluate IPI-549 both as a monotherapy and in combination with Opdivo. Infinity plans to report data from the monotherapy expansion and combination dose escalation components and initial data from the combination expansion component of the Phase 1/1b study of IPI-549 with Opdivo in the second quarter of 2018. In the second half of 2018, Infinity expects to report more mature clinical data from the combination expansion component of the study including translational insights from paired tumor biopsies across multiple diseases.

"2018 will be a decisive year for both Infinity and IPI-549, as we look forward to reporting maturing data from the Phase 1/1b trial both in monotherapy and in combination with Opdivo at several medical meetings throughout the year, which will help to define our development and regulatory strategy for this first-in-class product candidate," stated Adelene Perkins, Infinity’s chair and chief executive officer. "IPI-549 represents a unique approach to targeting tumors through its effects on myeloid cells within the tumor microenvironment, and we are very pleased with the data to date. There is a significant need for better treatment options for patients, especially for patients who do not respond to, or develop resistance to, existing immunotherapies, as well as for types of cancer where there is limited benefit from treatment with checkpoint inhibitors. We look forward to presenting updates throughout 2018 from our Phase 1/1b clinical trial."

"As the majority of patients treated with IPI-549 monotherapy have advanced forms of cancer and received several therapies prior to enrollment in this study, it’s very encouraging to see single-agent activity, including a patient with a partial response who has remained on treatment for over a year and continues on study today," said Dr. David Hong from MD Anderson Cancer Center, Deputy Chair of the Department of Investigational Cancer Therapeutic. "IPI-549 has also been well tolerated with a favorable safety profile."

Infinity’s chair and chief executive officer, Adelene Perkins, will discuss the company’s continued execution on its corporate strategy and 2018 priorities as part of a podium presentation at the 36th Annual J.P. Morgan Healthcare Conference on Thursday, January 11, at 9:30 a.m. PST (12:30 p.m. EST). The presentation will be webcast on Infinity’s website, www.infi.com.

Anticipated Milestones in 2018

During 2018, Infinity expects to achieve the following IPI-549 data milestones:

• Report data from the monotherapy expansion component of the study in the second quarter of 2018

• Report data from the combination dose-escalation component of the study in the second quarter of 2018
• Report initial data from the combination expansion component of the study in the second quarter of 2018

• Report additional data from the combination expansion component, with more mature clinical and translational data, including insights from paired tumor biopsies, in the second half of 2018
2018 Financial Guidance

Infinity ended 2017 with approximately $57.6 million in cash and investments (unaudited) and plans to report its fourth quarter and full-year 2017 financial results in March. The company is providing the following financial guidance today:

• Net Loss: Infinity expects net loss for 2018 to range from $40 million to $50 million.

• Cash and Investments: Infinity expects to end 2018 with a year-end cash and investments balance ranging from $10 million to $20 million.

• Based on its current operational plans, Infinity expects that its existing cash, cash equivalents and available-for-sale securities at December 31, 2017, will be adequate to satisfy the company’s capital needs into the first quarter of 2019.
Infinity’s financial guidance excludes additional funding or business development activities and does not include the potential $22 million payment from Verastem upon the first regulatory approval of duvelisib. Verastem has provided its expectation that it plans to submit a New Drug Application to the U.S. Food and Drug Administration for duvelisib in the first quarter of 2018.

About IPI-549

IPI-549 is an investigational first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage function and increasing anti-tumor macrophage function. In preclinical studies, IPI-549 reprograms macrophages from a pro-tumor (M2), immune suppressive function, to an anti-tumor (M1) immune activating function and can enhance the activity of, and overcome resistance to, checkpoint inhibitors.4 5 As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially additive or synergistic approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

The ongoing Phase 1/1b study being conducted by Infinity is designed to evaluate the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in approximately 200 patients with advanced solid tumors.6 The four-component study includes monotherapy and combination dose-escalation components, in addition to monotherapy expansion and combination expansion components. The monotherapy dose-escalation component is complete and the monotherapy expansion component has been fully enrolled. The combination dose-escalation component is also complete, and combination expansion cohorts are open to enrollment.

The combination expansion component of the study includes multiple cohorts designed to evaluate IPI-549 in patients with specific types of cancer, including patients with non-small cell lung cancer (NSCLC), melanoma, and head and neck squamous cell carcinoma (HNSCC) whose tumors show initial resistance or initially respond to but subsequently develop resistance to immune checkpoint blockade therapy. The combination expansion component also includes a cohort of patients with triple negative breast cancer (TNBC) who have not been previously treated with immune checkpoint blockade therapy, a cohort of patients with mesothelioma, a cohort of patients with adrenocortical carcinoma and a cohort of patients with high baseline levels of MDSCs.

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 8, 2018 Sanofi and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will accelerate and expand investment for the clinical development of the PD-1 (programmed cell death protein 1) antibody cemiplimab in oncology and dupilumab in Type 2 allergic diseases (Press release, Sanofi Genzyme, JAN 8, 2018, View Source [SID1234522976]). Both of these breakthrough therapies have the potential to benefit a number of different patient populations and this strategic investment will enable the companies to evaluate cemiplimab and dupilumab in broad clinical development programs.

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Under the terms of the expansion, the investment in cemiplimab will be increased to $1.64 billion, an increase of approximately $1 billion over the initial 2015 agreement and Sanofi and Regeneron will continue to equally fund cemiplimab development. The companies will also continue their investment in other immuno-oncology programs under their existing Immuno-oncology Discovery Agreement. Investigational cemiplimab is being studied as monotherapy and in combination with other therapies in a wide range of cancers including advanced skin cancers, non-small cell lung cancer, cervical cancer and lymphomas, with more studies in other indications planned to begin in 2018. The companies expect to submit U.S. and EU regulatory applications for cemiplimab in advanced cutaneous squamous cell carcinoma in the first quarter of 2018.

The additional investment in the dupilumab development program will help accelerate planned new studies in chronic obstructive pulmonary disease, peanut allergy and grass allergy as well as in patients who have multiple allergic conditions. These areas are in addition to ongoing dupilumab clinical development in pediatric atopic dermatitis, pediatric asthma, eosinophilic esophagitis and nasal polyposis. Dupixent (dupilumab) is approved for the treatment of adults with moderate-to-severe atopic dermatitis in the U.S. and EU and a U.S. supplemental biologics license application was submitted for uncontrolled, persistent asthma for patients aged 12 and over in the fourth quarter of 2017.

The additional investment will also accelerate and expand development of REGN3500, an IL-33 antibody, with studies expected to be conducted in atopic dermatitis, asthma and chronic obstructive pulmonary disease. The increased funding for dupilumab and REGN3500 will be pursuant to the existing Antibody License and Collaboration Agreement between the companies.

"The ongoing collaboration between Sanofi and Regeneron underscores our commitment to partnering in the development of medicines to treat significant unmet medical needs," said Elias Zerhouni, MD, Global Head of R&D at Sanofi. "The expansion of these clinical programs for both cempilimab and dupilumab should enable us to quickly identify treatment opportunities in other disease areas."

Regeneron has agreed to grant a limited waiver of the "lock-up" in the Amended and Restated Investor Agreement between the companies, so that Sanofi may sell a small percentage of the Regeneron common stock it owns to fund a portion of the cemiplimab and dupilumab development expansion. This waiver will allow Sanofi to sell in private transactions to Regeneron up to an aggregate of 1.4 million shares of Regeneron common stock through the end of 2020, representing approximately 6 percent of the 23.9 million shares of Regeneron common stock Sanofi currently owns. As of October 20, 2017 there were 107.4 million shares of Regeneron capital stock outstanding. If Regeneron decides not to purchase the shares, Sanofi will be allowed to sell those shares on the open market, subject to certain volume and timing limitations. Further details on the updated agreements are available in Regeneron’s current report on Form 8-K filed today.

Cemiplimab and dupilumab were invented by Regeneron using the company’s proprietary VelocImmune technology that yields optimized fully-human antibodies. Other than the approved uses of Dupixent, cemiplimab, Dupilumab, and REGN3500 are under clinical investigation and their safety and efficacy have not been fully evaluated by any regulatory authority.

On January 9, 2018 Amgen Astellas BioPharma K.K. (Headquarters Tokyo; President and Representative Director Steve Sugino "Amgen Astellas BioPharma") and Astellas Pharma Inc. (Headquarters Tokyo; President and CEO Yoshihiko Hatanaka "Astellas") reported that an application was submitted in Japan for the marketing authorization for bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct blinatumomab (Genetically Recombination) (generic name, development code: AMG 103, "blinatumomab") to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Astellas, JAN 8, 2018, View Source [SID1234522970]). In Japan, blinatumomab is jointly developed by Amgen Astellas BioPharma and Astellas.

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ALL affects approximately 5,000 patients in Japan1, out of which an estimated 670 per year have relapsed or refractory ALL2,3,4. There are several limitations to current treatment options, including their limited efficacy in adult and pediatric patients with relapsed or refractory ALL and dependency on a limited number of drugs with similar mechanisms of action. Improved outcomes for relapsed or refractory ALL patients calls for the development of drugs such as blinatumomab which demonstrate efficacy as a monotherapy and have mechanisms of action dissimilar to cytotoxic agents.

The submission of application for marketing approval in Japan was based on the results from multiple global clinical studies including the Phase 3 randomized study (TOWER study), and the Japanese Phase 1b/2 study. In the TOWER study, blinatumomab was shown to extend overall survival compared to standard-of-care (SOC) chemotherapy in adult patients with relapsed or refractory ALL. Blinatumomab is considered to have the potential to address the serious unmet medical needs of ALL patients.

Blinatumomab received Orphan Drug designation from the Ministry of Health, Labour and Welfare effective September 29, 2017.

About Blinatumomab

Blinatumomab (genetically recombinant antibody) is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. Blinatumomab was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration, and is now approved in the U.S. for the treatment of relapsed or refractory B-cell precursor ALL in adult and pediatric patients. In November 2015, the EU granted conditional marketing authorization for blinatumomab for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. AmgenInc. is seeking to gain approval for blinatumomab in countries around the world.

TOWER Study

The TOWER study was a Phase 3 randomized study investigating the efficacy of blinatumomab versus SOC chemotherapy in 405 adult patients with Ph- relapsed or refractory B-cell precursor ALL. The study enrolled a difficult-to-treat patient population, which included patients from several stages of relapse. In the blinatumomab arm, this included 35% of patients that had relapsed post-allogenic hematopoietic stem cell transplant (alloHSCT), and excluded those with late first relapse (≥ 12 months after initial remission). Patients were randomized in a 2:1 ratio to receive blinatumomab (n = 271) or one treatment with investigator’s choice out of 4 types of SOC chemotherapy regimens (n = 134). The determination of efficacy was based on overall survival. Per the recommendation of the data monitoring committee, the study was ended early for evidence of superior OS in the blinatumomab arm vs SOC chemotherapy from the pre-specified interim analysis.

These results are published in the New England Journal of Medicine.5

About BiTE Technology

Bispecific T cell engager (BiTE) antibody constructs are being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

About Amgen’s Commitment to Oncology

Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.