Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice

On August 30, 2017 – Novartis announced today that the US Food and Drug Administration (FDA) has approved Kymriah(TM)(tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient’s own T cells to fight cancer (Press release, Novartis, AUG 30, 2017, View Source [SID1234520344]). Kymriah is the first therapy based on gene transfer approved by the FDA.

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"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."

"We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program," said Bruno Strigini, CEO of Novartis Oncology. "As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated."

The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.

There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years [2], [3].

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients’ lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine, who is a pioneer of this new treatment. "Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types."

In close collaboration with Novartis and Penn, Children’s Hospital of Philadelphia (CHOP) was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial.

"Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and durable remission in children and young adults with relapsed or refractory B-cell ALL," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program at Children’s Hospital of Philadelphia (CHOP). "We’ve never seen anything like this before and I believe this therapy may become the new standard of care for this patient population."

Novartis is committed to ensuring eligible patients have access to Kymriah, and is working to ensure payers understand the value of Kymriah and provide coverage for patients. To address the unique aspects of the therapy, Novartis has also developed various patient access programs to support safe and timely access for patients. Novartis is also providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured.

Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.

Groundbreaking Collaboration with the Centers for Medicare and Medicaid Services
Novartis also announced a novel collaboration with the United States Centers for Medicare and Medicaid Services (CMS) focused on improving efficiencies in current regulatory requirements in order to deliver value-based care and ensure access for this specific patient population.

This approach is intended to include indication-based pricing for medicines and supports payments for a medicine, such as Kymriah for its initial indication, based on the clinical outcomes achieved, which would eliminate inefficiencies from the healthcare system. Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion.

Furthermore, Novartis is collaborating with CMS to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach.

"Novartis has been at the forefront of outcomes-based pricing and is very pleased to work with CMS on this first-of-its-kind collaboration with a technology that has the potential to transform cancer care," said Joseph Jimenez, CEO of Novartis. "We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states."

Immune Design Announces New CMB305 + Checkpoint Inhibitor Topline Data from an Upcoming Presentation at the ESMO 2017 Congress

On August 30, 2017 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported positive topline data from its interim analysis of the ongoing, randomized Phase 2 trial evaluating CMB305 in combination with atezolizumab (TECENTRIQ) or atezolizumab alone in 88 soft tissue sarcoma patients (Press release, Immune Design, AUG 30, 2017, View Source [SID1234520357]). The data will be presented in a poster discussion session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress, September 8-12, 2017 in Madrid, Spain.

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"The two main goals of this study are (1) to determine whether combining a next-generation vaccine like CMB305 with a checkpoint inhibitor (such as an anti-PD-L1 antibody) provides improved clinical benefit compared to that of the checkpoint inhibitor alone, particularly in a PD-L1-low or -negative tumor, and (2) in a randomized setting, to determine the biological activity of CMB305," said Carlos Paya, M.D., Ph.D., President and Chief Executive Officer of Immune Design. "We believe these interim data constitute the first steps towards answering both questions in a favorable manner."

Data to be presented at ESMO (Free ESMO Whitepaper) build upon those data on the first 36 patients summarized in the abstract, and include a greater number of patients enrolled.

Clinical Benefit: Data from the larger patient population show that patients receiving CMB305 and atezolizumab experienced greater clinical benefit in the form of Disease Control Rate (including objective responses), Progression Free Survival and Time to Next Treatment than those receiving atezolizumab alone.
Immune Response: Patients who received the combination of CMB305 and atezolizumab demonstrated an increased frequency of induced immune responses to NY-ESO-1, including NY-ESO-1-specific T cells, NY-ESO-1 antibodies, and antigen spreading, in comparison to patients who received atezolizumab alone
Biomarkers: In an exploratory analysis, a trend towards improved overall survival was observed in patients in the CMB305 and atezolizumab combination arm who had pre-existing and treatment-induced anti-NY-ESO-1 immunity, compared to the atezolizumab alone arm. Pre-treatment tumor biopsy analysis showed negligible levels of PD-L1 expression.
Safety: No new safety signals have been observed in either arm.
The fully enrolled trial is evaluating the safety, immunogenicity and efficacy of CMB305 in combination with atezolizumab, or atezolizumab alone, in a total of 88 patients with locally advanced, relapsed, or metastatic NY-ESO-1+ synovial sarcoma or myxoid/round-cell liposarcoma. Atezolizumab is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1) and is being developed by Genentech, a member of the Roche Group. The trial is being conducted pursuant to a clinical collaboration with Genentech. Immune Design intends to present survival data in 2018 once all patients have at least one year of follow up (current data are preliminary: median duration of observation

The ESMO (Free ESMO Whitepaper) Poster Discussion session presentation details are as follows:

A Phase 2 Study of CMB305 and Atezolizumab in NY-ESO-1+ Soft Tissue Sarcoma: Interim Analysis of Immunogenicity, Tumor Control and Survival
Abstract # 1480PD
Session Title: Sarcoma Poster Discussion Session
Date: Monday, Sept. 11, 2017
Time: 11 a.m. — 12:30 p.m.
Location: Bilbao Auditorium
Poster Presenter: Dr. Sant Chawla
Poster Discussant: Dr. Robert Maki

About CMB305

CMB305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors, designed to generate an integrated, anti-NY-ESO-1 immune response in vivo via a targeted, specific interaction with dendritic cells, a mechanism of action Immune Design believes differs from traditional cancer vaccines. CMB305 is being evaluated in soft tissue sarcoma patients in ongoing Phase 1 monotherapy and 2 combination studies. Immune Design has received Orphan Drug Designation for CMB305 from the U.S. Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma, as well as from the FDA and European Medicines Agency for each of the components of CMB305 for the treatment of soft tissue sarcoma.

Cancer Research Online Crowdsourcing Campaign Passes 78% of Funding Goal

On August 29, 2017 Augustus BioTarget reported that An early-stage drug development company in South Carolina has launched an online fundraising campaign to study the ancient spice curcumin in combination with an FDA-approved Immune Checkpoint Inhibitor to fight colon cancer (Press release, Augustus BioTarget, AUG 29, 2017, http://augustusbiotarget.com/wp-content/uploads/2017/08/Press-Release-ABT-August-29-2017.pdf [SID1234556207]).

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Within five days of launch, the company has met 78% of its funding goal on Experiment.com, an online science crowdfunding platform dedicated to scientific research. https://experiment.com/curcumincancerproject

A group of scientists working in the US at Augustus BioTarget, Inc., and in Germany at Rodos Biotarget, GmbH, developed a unique nanocarrier drug delivery system, the CLR-TargoSphere, into which curcumin was encapsulated. This will be studied in mice with colon cancer at the Charles River Labs in North Carolina.

"Our aim is to resurrect the immune response against cancer with targeted curcumin," said Michael Scolaro, founder of Augustus BioTarget and Chief Investigator. "Curcumin is known to possess significant anti-inflammatory and anti-neoplastic properties. But because it is very poorly absorbed and distributed in the body, it has been impractical for clinical use. Delivering curcumin directly to immune cells that are immobilized by cancers promises to help restore anticancer activity.

"Using curcumin in medicine may not secure huge capital investments the way a new iPad does," he added. ‘But with the latest advancements in immune system targeting, its use to fight cancer is now within reach."

Jazz Pharmaceuticals and ImmunoGen, Inc. Announce a Strategic Collaboration and Option Agreement to Develop and Commercialize
Antibody-Drug Conjugate Products

On August 29, 2017 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and ImmunoGen, Inc. (Nasdaq: IMGN) reported that the companies have entered into a collaboration and option agreement granting Jazz Pharmaceuticals exclusive, worldwide rights to opt into development and commercialization of two early-stage, hematology-related antibody-drug conjugate (ADC) programs, as well as an additional program to be designated during the term of the agreement (Press release, ImmunoGen, AUG 29, 2017, View Source [SID1234520331]). The programs covered under the agreement include IMGN779, a CD33-targeted ADC for the treatment of acute myeloid leukemia (AML) in Phase 1 testing, and IMGN632, a CD123-targeted ADC for hematological malignancies expected to enter clinical testing before the end of the year.

Under the terms of the agreement, ImmunoGen will be responsible for the development of the three ADC programs prior to any potential opt-in by Jazz. Following any opt-in, Jazz would be responsible for any further development as well as for potential regulatory submissions and commercialization.

As part of the agreement, Jazz will pay ImmunoGen an upfront payment of $75 million. Additionally, Jazz will pay ImmunoGen up to $100 million in development funding over seven years to support the three ADC programs. For each program, Jazz may exercise its opt-in right at any time prior to a pivotal study or any time prior to a biologics license application (BLA) upon payment of an option exercise fee of mid-double digit millions or low triple digit millions, respectively. For each program to which Jazz elects to opt-in, ImmunoGen would be eligible to receive milestone payments based on receiving regulatory approval of the applicable product, plus tiered royalties as a percentage of commercial sales by Jazz, which depending upon sales levels and the stage of development at the time of opt-in, range from mid- to high single digits in the lowest tier to low 10’s to low 20’s in the highest tier. After opt-in, Jazz and ImmunoGen would share costs associated with developing and obtaining regulatory approvals of the applicable product in the United States (U.S.) and the European Union. ImmunoGen has the right to co-commercialize in the U.S. one product (or two products, under certain limited circumstances) with U.S. profit sharing in lieu of Jazz’s payment of the U.S. milestone and royalties to ImmunoGen.

"We are pleased to enter into this collaboration with ImmunoGen, a well-known leader in the field of ADC technology, with demonstrated success in creating ADC molecules, including the only FDA-approved ADC product to treat metastatic breast cancer. This investment supports our long-term commitment to expand our hematology/oncology portfolio with the potential addition of multiple innovative antibody drug conjugates," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "We look forward to the advancement of these ADC programs and the potential synergy of these compounds with our current products and pipeline, as new therapeutic options for cancer patients are urgently needed."

"This strategic partnership with Jazz significantly advances our goal of accelerating the development of our early-stage novel ADC assets. This deal joins us with a global partner, provides us with substantial funding to support these programs, and preserves the right to co-commercialize one of these assets," said Mark Enyedy, president and chief executive officer of ImmunoGen. "Jazz has demonstrated the ability to bring innovative compounds to patients and will make an ideal partner to help develop and commercialize our novel ADC assets targeting AML, and more broadly, in the area of hematology/oncology. In addition, this partnership significantly strengthens our financial position and moves us closer to delivering upon our mission of bringing ADC therapies to patients."

IMGN779 is a novel ADC that combines a high-affinity, humanized anti-CD33 antibody, a cleavable disulfide linker, and one of ImmunoGen’s novel indolino-benzodiazepine payloads, called IGNs, which alkylate DNA without crosslinking, resulting in potent preclinical anti-leukemia activity with relative sparing of normal hematopoietic progenitor cells(1),(2). IMGN779 is in Phase 1 clinical testing for the treatment of AML. IMGN632 is a preclinical stage humanized anti-CD123 antibody-based ADC that is a potential treatment for AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN), myelodysplastic syndrome, B-cell acute lymphocytic leukemia, and other CD123-positive malignancies. IMGN632 uses a novel payload, linker, and antibody technology and in AML xenograft models has demonstrated a large therapeutic index(3). ImmunoGen expects to file an investigational new drug application (IND) for IMGN632 this quarter and enroll the first patient in a Phase 1 study before the end of the year.

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Thermo Fisher Scientific Completes Acquisition of Patheon

On August 29, 2017 /PRNewswire/ — Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported that it has completed its acquisition of Patheon N.V. (NYSE: PTHN), a leading contract development and manufacturing organization (CDMO) serving the pharmaceutical and biotechnology sectors, for approximately $7.2 billion (Press release, Thermo Fisher Scientific, AUG 29, 2017, View Source [SID1234520333]). Today’s close follows the expiration of Thermo Fisher’s initial tender offer for Patheon at $35.00 per share in cash.

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"We’re pleased to complete our acquisition of Patheon and look forward to the significant value this transaction will create for our customers and our shareholders," said Marc N. Casper, president and chief executive officer of Thermo Fisher Scientific. "By adding Patheon’s highly complementary CDMO capabilities to our leading clinical trials services and bioproduction technologies, we will be an even stronger partner for our pharmaceutical and biotech customers. We’re delighted to welcome our Patheon colleagues to the Thermo Fisher team and excited about the new opportunities we have to help our customers accelerate innovation and enhance productivity by leveraging our combined strengths."

Patheon generated fiscal 2016 revenue of approximately $1.9 billion and will become part of Thermo Fisher’s Laboratory Products and Services Segment. For the remainder of 2017, the transaction is expected to be approximately $0.09 accretive to adjusted earnings per share1, which includes $0.02 in the third quarter. Details of the 2017 impact will be provided during Thermo Fisher’s third quarter earnings call in late October.

Thermo Fisher continues to expect to realize total synergies of approximately $120 million by year three following the close, consisting of approximately $90 million of cost synergies and approximately $30 million of adjusted operating income benefit from revenue-related synergies.

Further Transaction Details and Timing

Today, Thermo Fisher is acquiring approximately 95.3% of Patheon’s outstanding ordinary shares.

The initial offering period for the tender offer and withdrawal rights expired at 5:00 p.m., New York City time, on August 28, 2017 (the "Expiration Time"). Based on information provided by American Stock Transfer & Trust Company, LLC, the depositary for the tender offer, a total of 138,406,058 Patheon ordinary shares, representing approximately 95.3% of the outstanding Patheon ordinary shares, had been validly tendered and had not been properly withdrawn as of the Expiration Time (excluding 176,509 ordinary shares, representing approximately 0.12% of the aggregate number of ordinary shares outstanding, tendered pursuant to guaranteed delivery procedures that have not yet been delivered in settlement or satisfaction of such guarantee). Thermo Fisher’s wholly owned subsidiary, Thermo Fisher (CN) Luxembourg S.à r.l., has accepted for payment all shares that were validly tendered and were not properly withdrawn as of the Expiration Time, and payment for such shares will be made promptly in accordance with the terms of the offer.

Thermo Fisher also announced the commencement of a subsequent offering period scheduled to expire at 12:01 a.m., New York City time, on September 13, 2017, as more fully described in the tender offer statement on Schedule TO filed by Thermo Fisher with the U.S. Securities and Exchange Commission (the "SEC") on May 31, 2017 (as amended and supplemented, the "Schedule TO"). All ordinary shares validly tendered during the subsequent offering period will be immediately accepted for payment, and tendering holders will thereafter promptly be paid the same form and amount of offer consideration as in the initial offering period. The procedures for tendering shares during the subsequent offering period are described in the Schedule TO and are generally the same as those applicable to the initial offering period, except that the guaranteed delivery procedures may not be used during the subsequent offering period and no withdrawal rights will apply to shares tendered during the subsequent offering period.

Patheon has requested that the New York Stock Exchange (the "NYSE") suspend trading of Patheon ordinary shares after the close of business on September 1, 2017, and Patheon intends to file a Form 25, Notification of Removal from Listing and/or Registration under Section 12(b) of the U.S. Securities Exchange Act of 1934, as amended (the "Exchange Act") with the SEC on such date. Patheon also intends to terminate its reporting obligations under the Exchange Act by filing a Form 15 with the SEC on or about September 11, 2017. Following delisting from the NYSE, Patheon ordinary shares will not be listed or registered on another national securities exchange. Delisting is likely to reduce significantly the liquidity and marketability of any Patheon ordinary shares that have not been tendered pursuant to the tender offer.

Advisors

Goldman Sachs & Co. acted as financial advisor to Thermo Fisher, and Wachtell, Lipton, Rosen & Katz served as legal counsel.

Morgan Stanley & Co. acted as financial advisor to Patheon, and Skadden, Arps, Slate, Meagher & Flom LLP served as legal counsel.

Use of Non-GAAP Financial Measures

In addition to the financial measures prepared in accordance with generally accepted accounting principles (GAAP), we use certain non-GAAP financial measures, including adjusted earnings per share (EPS) and adjusted operating income, which exclude certain acquisition-related costs, including charges for the sale of inventories revalued at the date of acquisition and significant transaction costs; restructuring and other costs/income; and amortization of acquisition-related intangible assets. Adjusted EPS also excludes certain other gains and losses that are either isolated or cannot be expected to occur again with any regularity or predictability, tax provisions/benefits related to the previous items, benefits from tax credit carryforwards, the impact of significant tax audits or events and the results of discontinued operations. We exclude the above items because they are outside of our normal operations and/or, in certain cases, are difficult to forecast accurately for future periods. Thermo Fisher does not provide GAAP financial measures on a forward-looking basis because we are unable to predict with reasonable certainty and without unreasonable effort items such as the timing and amount of future restructuring actions and acquisition-related charges as well as gains or losses from sales of real estate and businesses, the early retirement of debt and the outcome of legal proceedings. The timing and amount of these items are uncertain and could be material to Thermo Fisher’s results computed in accordance with GAAP. These non-GAAP projections should not be considered a substitute for GAAP measures.