On October 12, 2017 The National Institutes of Health and 11 leading biopharmaceutical companies reported that it launched the Partnership for Accelerating Cancer Therapies (PACT), a five-year public-private research collaboration totaling $215 million as part of the Cancer Moonshot (Press release, US NIH, OCT 12, 2017, View Source [SID1234520878]). PACT will initially focus on efforts to identify, develop and validate robust biomarkers — standardized biological markers of disease and treatment response — to advance new immunotherapy treatments that harness the immune system to attack cancer. The partnership will be managed by the Foundation for the National Institutes of Health (FNIH), with the Food and Drug Administration serving in an advisory role.

“This new public-private partnership is a significant step forward in the battle against cancer and a real boost to the potential of immunotherapy,” said Acting Health and Human Services Secretary Eric Hargan. “We are excited for this partnership, which will strengthen efforts already underway across HHS.”

New immunotherapies have resulted in dramatic responses in certain cancer cases. They have also been the focus of intense investment by biopharmaceutical companies seeking to provide new options for patients who do not respond to other cancer therapies, but they don’t work for all patients. Development and standardization of biomarkers to understand how immunotherapies work in some patients, and predict their response to treatment, are urgently needed for these therapies to provide benefit to the maximum number of people.

“We have seen dramatic responses from immunotherapy, often eradicating cancer completely for some cancer patients,” said NIH Director Francis S. Collins, M.D., Ph.D. “We need to bring that kind of success — and hope — for more people and more types of cancers, and we need to do it quickly. A systematic approach like PACT will help us to achieve success faster.”

PACT will facilitate systematic and uniform clinical testing of biomarkers to advance our understanding of the mechanisms of response and resistance to cancer therapy. The research conducted under the partnership will also integrate immune and other related oncology biomarkers into clinical trials by defining a set of standardized biomarkers to be tested across a variety of studies. This approach will allow for consistent generation of data, uniform and harmonized assays to support data reproducibility, comparability of data across trials, and discovery and validation of new biomarkers for immunotherapy and related combinations. PACT will also facilitate information sharing by all stakeholders to better coordinate clinical efforts, align investigative approaches, reduce duplication and enable more high-quality trials to be conducted.

“A scientific and organizational challenge this complex cannot be addressed effectively by any one organization acting alone,” said Maria C. Freire, Ph.D., President and Executive Director of the FNIH. “Instead, it requires the energies and resources of public and private partners working in close collaboration.”

PACT partners include AbbVie, North Chicago, Illinois; Amgen, Thousand Oaks, California; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; Bristol-Myers Squibb, New York; Celgene Corporation, Summit, New Jersey; Genentech, a member of the Roche Group, San Francisco; Gilead Sciences, Foster City, California; GlaxoSmithKline plc, Brentford, United Kingdom; Janssen Pharmaceutical Companies of Johnson & Johnson, New Jersey; Novartis Institutes for Biomedical Research, Basel, Switzerland; and Pfizer, Inc., New York. (See what the partner organizations are saying about PACT). Additional support has been provided by the Pharmaceutical Research and Manufacturers Association (PhRMA). The 11 partner organizations will contribute up to $1 million per year for five years through the FNIH for a total private sector contribution of $55 million. NIH will contribute $160 million over the five years of the partnership, pending availability of funds.

NIH’s National Cancer Institute (NCI) recently awarded cooperative agreements to support four Cancer Immune Monitoring and Analysis Centers (CIMACs) and a Cancer Immunologic Data Commons (CIDC) with a total of $53.6 million in funding over five years. The four CIMACs and one CIDC will form a network of laboratory centers that will support both adult and pediatric immunotherapy trials. Researchers at the CIMACs will perform deep tumor and immune profiling. The resulting data will be collected in the CIDC database for exploration of biomarkers of immune response. This network will also provide a foundation for the core laboratory, assay development and database functions required by PACT.

“NCI’s long-term support for basic and translational research in immunotherapy paved the way for the recent dramatic clinical successes in this area,” said Douglas R. Lowy, M.D., Acting Director of NCI. “This partnership, and the data the partners have committed to making publicly accessible to the broader research community, will facilitate our continued progress in helping to find the cancer treatments that benefit the greatest number of patients.”

The NCI cooperative agreements have been awarded to Dana-Farber Cancer Institute, Boston (CIMAC and CIDC); Stanford Cancer Institute, Stanford, California (CIMAC); Precision Immunology Institute and the Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, New York (CIMAC) and University of Texas MD Anderson Cancer Center, Houston (CIMAC).

On October 12, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI) (Karyopharm) and Ono Pharmaceutical Co., Ltd. (ONO), reported their entry into an exclusive license agreement for the development and commercialization of selinexor, Karyopharm’s lead, novel, oral Selective Inhibitor of Nuclear Export (SINE) compound, and KPT-8602, Karyopharm’s second-generation oral SINE compound (Press release, Karyopharm, OCT 12, 2017, View Source [SID1234520877]). The agreement includes the development of selinexor and KPT-8602 for the diagnosis, treatment and/or prevention of all human oncology indications in Japan, South Korea, Taiwan, Hong Kong, and ASEAN countries (the Territory).

Under the terms of the agreement, Karyopharm will receive a one-time upfront payment of ¥2.5 billion (approximately US$22.3 million) from ONO and retains all rights to selinexor and KPT-8602 outside the Territory. Karyopharm is eligible to receive up to an additional ¥19.15 billion (approximately US$170.7 million at the current exchange rate) if specified future development and commercial milestones are achieved by ONO. Karyopharm is also eligible to receive low double-digit royalties based on future net sales of selinexor and KPT-8602 in the Territory. In exchange, ONO will receive exclusive rights to develop and commercialize both compounds in the Territory, at its own cost and expense. ONO will also have the ability to participate in any global clinical study of selinexor and KPT-8602, and will bear the cost and expense for patients enrolled in clinical studies in the Territory.

“We are very delighted to collaborate on the development of selinexor and KPT-8602, an early development stage XPO-1 inhibitor with Karyopharm, a leading pharmaceutical company focused on the research and development of novel first-in-class drugs in the oncology field,” said Gyo Sagara, President, Representative Director of ONO. “We believe both products will present a new treatment option to patients suffering from devastating cancers in Asian countries.”

“Given ONO’s established leadership in oncology, including Opdivo (nivolumab) and Kyprolis (carfilzomib) in Japan, we believe there is no company better suited to advance both selinexor and KPT-8602 in Japan and the other licensed territories,” said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. “ONO is well-known and widely respected for its clinical development and commercial expertise, and this partnership provides important validation for both compounds, while allowing us to remain focused on executing our late-phase selinexor trials and pursue regulatory approval in the United States and European Union. We look forward to working with the ONO team to advance both compounds with the goal of rapidly bringing them to patients who are in need of new treatment options.”

About Selinexor
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,200 patients have been treated with selinexor, and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

About KPT-8602
KPT-8602 is a second generation oral SINE compound. KPT-8602 functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. KPT-8602 has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects.
About Karyopharm Therapeutics

On October 12, 2017 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that an abstract describing new data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), has been selected as a late-breaking presentation during an oral session at the 2017 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting taking place in National Harbor, MD, November 10 – 12 (Press release, Infinity Pharmaceuticals, OCT 12, 2017, View Source [SID1234520876]). Additionally, a clinical trials in progress poster will also be presented on the Phase 1/1b clinical study which is ongoing to explore the safety and activity of IPI-549 both as a monotherapy and in combination with Opdivo (nivolumab), a PD-1 immune checkpoint inhibitor, in patients with advanced solid tumors. IPI-549 is believed to be the only PI3K-gamma inhibitor in clinical development.

Details of the presentations are as follows:

Updated Phase 1/1b Data
Title: Monotherapy dose escalation clinical and translational data from first-in-human study in advanced solid tumors of IPI-549, an oral, selective, PI3K-gamma inhibitor targeting tumor macrophages
Abstract number: O43
Oral session: Clinical Trials – New Agents
Oral session date and time: Friday, November 10, 2017, from 1:45 p.m. –3:30 p.m. ET
Lead author: David Hong, M.D., Deputy Chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Additionally, an identically titled poster will be presented on Friday, November 10, 2017, from 12:30 p.m. – 2:00 p.m. ET and 6:30 p.m. – 8:00 p.m. ET.

Clinical Trials in Progress
Title: Phase 1/1b, first-in-human study of the PI3K-gamma inhibitor IPI-549 as monotherapy and combined with nivolumab in patients with advanced solid tumors
Abstract number: P219
Poster session: Clinical trials in progress
Presentation time: Friday, November 10, 2017, from 12:30 p.m. – 2:00 p.m. ET and 6:30 p.m. – 8:00 p.m. ET
Lead author: Antoni Ribas, M.D., Ph.D., Parker Institute Center Director at the University of California, Los Angeles (UCLA)

About the IPI-549 and the Ongoing Phase 1 Study
IPI-549 is an investigational, orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 reprograms macrophages from a pro-tumor, M2, to an anti-tumor, M1, phenotype and is able to overcome resistance to checkpoint inhibition as well as to enhance the activity of checkpoint inhibitors.1,2 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 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.3 The four-part study includes monotherapy and combination dose-escalation components, in addition to monotherapy expansion and combination expansion components. Patient enrollment is complete in monotherapy dose-escalation, and monotherapy expansion is ongoing. Combination dose-escalation is also ongoing, and combination expansion is expected to begin in the second half of 2017.

The combination expansion component 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 subsequently develop resistance to immune checkpoint blockade therapy. This combination expansion will also include a cohort of patients with triple negative breast cancer (TNBC) who have not been previously exposed to immune checkpoint blockade therapy. Although there has been great progress in the treatment of cancer, there remains a need for additional treatment options. NSCLC, melanoma, HNSCC and TNBC account for more than 22 percent of all new cancer cases in the U.

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

On October 12, 2017 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies, reported that the first patient was dosed in the phase 1 clinical study of its oncology asset MP0274. MP0274 is a proprietary DARPin drug candidate for the treatment of HER2-positive cancer with a new mode of action compared to current standard of care antibodies (Press release, Molecular Partners, OCT 12, 2017, View Source [SID1234520868]).

The phase 1 study of MP0274 is a two part study in patients with advanced HER2-positive solid tumors. Part 1 will be conducted in three sites in Germany, Switzerland and the UK all of which are open to recruitment, and will assess safety, tolerability, pharmacokinetics and establish the recommended dose for further development. Part 2 will be conducted in the initial three sites as well as in additional sites and is designed to confirm safety and to assess preliminary efficacy at the recommended dose. Initial safety data are expected in the first half of 2018 and initial efficacy data towards the end of 2018.

“We are very pleased to have reached this important milestone to dose the first patient in our phase 1 study for patients with advanced HER-2 positive solid tumors with our novel drug candidate MP0274,” commented Dr. Andreas Harstrick, Chief Medical Officer at Molecular Partners. “With this milestone, Molecular Partners significantly expands its clinical portfolio besides the ongoing MP0250 clinical trials.”

Financial Calendar October 26, 2017 Q3 2017 Management Statement October 31, 2017 Extraordinary General Meeting November 9, 2017 R&D Day in New York February 8, 2018 Publication of Full-year Results 2017 (unaudited) March 16, 2018 Expected Publication of 2017 Annual Report April 18, 2018 Annual General Meeting View Source

About the DARPin Difference DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multispecificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.

With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan. Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and has entered into Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated T790M-positive NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has just moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

On October 12, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported that financial results for the company’s third quarter ended September 30, 2017 will be released on Wednesday, November 1, 2017 (Press release, Foundation Medicine, OCT 12, 2017, View Source [SID1234520898]). The management team will host a conference call on Wednesday, November 1, 2017, at 4:30 p.m. ET to discuss the company’s financial results and recent developments. The call can be accessed by dialing 1-877-270-2148 (domestic) or 1-412-902-6510 (international) five minutes prior to the start of the call. A passcode is not required to access the live call from either number. A replay of the conference call will be available until November 15, 2017 and can be accessed by dialing 1-412-317-0088 and providing the passcode 10113366.

The live, listen-only webcast of the conference call may be accessed by visiting the investors’ section of the company’s website at investors.foundationmedicine.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the company’s website for two weeks following the call.