On January 8, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported initial safety data from its two ongoing pilot studies of SPEAR T-cells targeting MAGE-A10, one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers (Press release, Adaptimmune, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325398 [SID1234522943]).

To date, 8 patients have each received 100 million transduced MAGE‑A10 SPEAR T-cells in the first dose cohorts of both studies. No evidence of toxicity related to off-target binding or alloreactivity has been observed. There have been no reports of neurotoxicity safety events similar to CAR‑T cell-related encephalopathy syndrome (CRES)1. In the NSCLC study, there has been one serious adverse event of cytokine release syndrome (CRS), a Grade 4 event that resolved with treatment. This event led to cohort 1 expansion from 3 to 6 patients. No dose limiting toxicities were observed in cohort 1 of the triple tumor study.

Following review by the independent safety review committee (SRC), the decision has been made to escalate to the next dose of 1 billion transduced MAGE-A10 SPEAR T-cells in the triple tumor study. This was the therapeutic threshold dose observed with SPEAR T‑cells targeting NY-ESO in the synovial sarcoma pilot study. The decision to escalate in the NSCLC cohort will be reviewed by the SRC following dosing of the 6th patient.

"These safety results, with one of our wholly-owned SPEAR T-cell treatments, and the upcoming escalation to the next dose in the triple tumor study are significant as they allow us to progress treating patients in these studies at a potentially active cell dose," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "As data accumulate throughout 2018, we will continue to share meaningful safety and efficacy data from the MAGE-A10 and MAGE-A4 programs at relevant scientific venues."

Details about Ongoing Trials with SPEAR T-cells Targeting MAGE-A10
There are two ongoing clinical trials with SPEAR T-cells targeting MAGE-A10; one in non-small cell lung cancer (NSCLC), and a triple tumor study in bladder, melanoma, and head & neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen. The three doses being evaluated are 100 million, 1 billion and 1 to 5 billion transduced SPEAR T-cells.

NSCLC study: In this study, five patients have received SPEAR T-cells in the first group of Cohort 1 (1a without fludarabine) 2, and there was one report of Grade 4 CRS that resolved with treatment.

Triple Tumor Study: Three patients have been dosed in the first cohort. There were no reports of CRS greater or equal to Grade 3, and all cases resolved with supportive treatment.

On January 8, 2018 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) reported a business update, including preliminary unaudited fourth quarter and full year 2017 financial results and 2018 financial guidance (Press release, AMAG Pharmaceuticals, JAN 8, 2018, View Source [SID1234522984]). The company will present further details at the 36th Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 9, 2018 at 10:00 a.m. PT (1:00 p.m. ET). A live audio webcast of the presentation and following breakout session will be accessible through the Investors section of AMAG’s website at www.amagpharma.com.

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William Heiden, AMAG’s president and chief executive officer, said, "Over the last few years we have transformed AMAG from a one product company into a company with five marketed products and two additional products in development. Today we are reporting double-digit revenue growth in 2017 of more than $600 million, along with strong bottom-line cash generation. Throughout the year, we also achieved many important goals that will be key to our long-term success, including the establishment of our new 200-person women’s health commercial team, the launch of Intrarosa (prasterone), a novel women’s health product, and the filing of supplemental new drug applications to extend our Makena and Feraheme brands."

"Our flexible operating plan supports the 2018 top-line revenue and adjusted EBITDA guidance ranges provided today, which incorporate the opportunities and key risks across our product portfolio. 2018 promises to be an exciting year for AMAG with many key value drivers ahead of us, including potential FDA approvals of the Makena subcutaneous auto-injector and the Feraheme broad label, as well as building on the successful launch of Intrarosa, with approximately 20,000 total prescriptions already written by more than 4,200 healthcare providers since our July 2017 launch," Mr. Heiden concluded.

Preliminary Fourth Quarter and Full Year 2017 Financial Results (unaudited)
Fourth Quarter 2017
AMAG expects total GAAP revenue for the fourth quarter of 2017 to be between $155 million and $162 million, representing approximately 5% growth over the same period in 2016. This includes Makena (hydroxyprogesterone caproate injection) net product sales of between $97 million and $102 million, Feraheme (ferumoxytol) injection and MuGard net product sales of between $26 million and $28 million, Intrarosa (launched in July 2017) net product sales of approximately $2 million, and Cord Blood Registry (CBR) service revenue of approximately $30 million.

AMAG expects total fourth quarter 2017 total non-GAAP revenue to be between $156 million and $163 million, which reflects a $1.4 million purchase accounting adjustment related to CBR deferred revenue.

For the fourth quarter of 2017, AMAG expects an operating loss of between $6 million and $16 million and adjusted EBITDA of between $58 million and $68 million.1

Full Year 2017
AMAG expects 2017 total GAAP revenue to be between $607 million and $614 million, representing 15% growth over 2016. This includes Makena net product sales of between $385 million and $390 million, Feraheme and MuGard net product sales of between $106 million and $108 million, Intrarosa net product sales of approximately $2 million, and CBR service revenue of approximately $114 million.

AMAG expects 2017 total non-GAAP revenue to be between $613 million and $620 million, which reflects a $5.5 million purchase accounting adjustment related to CBR deferred revenue.

For the full year of 2017, AMAG expects an operating loss of between $292 million and $302 million (due primarily to a third quarter non-cash accounting charge) and adjusted EBITDA of between $220 million and $230 million, the higher end of the guidance range.

In 2017, AMAG reduced total debt by approximately 20%, extended average debt maturities, and repurchased and retired approximately 1.4 million shares in the fourth quarter at an average price of $14.27 per share.

The company ended 2017 with approximately $329 million in cash and investments and total debt (principal amount outstanding) of approximately $815 million. In late February 2018, the company expects to report final financial results for the fourth quarter and audited results for full year of 2017.

2018 Financial Guidance
The company is providing the following financial guidance for 2018. This guidance encompasses management’s current assumptions about the potential impact of multiple opportunities and risks across AMAG’s product portfolio, including various potential outcomes of the pending FDA submissions for the Makena subcutaneous auto-injector and the Feraheme label expansion, as well as the entrance of generics to compete with the Makena intramuscular formulation in 2018.

$ in millions 2018 GAAP Guidance 2018 Non-GAAP Guidance
Total revenue $500 – $560 $500 – $560
Operating loss ($147) – ($117) N/A
Adjusted EBITDA N/A $100 – $130

2018 Key Dates and Priorities
•
February 2, 2018: PDUFA date for the expansion of the Feraheme label beyond the current chronic kidney disease (CKD) indication to include all eligible adult patients with iron deficiency anemia (IDA); prepare for first quarter 2018 potential approval and subsequent launch;
•
February 3, 2018: loss of Makena orphan drug exclusivity – While the company is currently ready with a partner to launch its own authorized generic to the intramuscular formulation (IM) as early as February, the company believes that a generic competitor may not enter the market until later in 2018;
•
February 14, 2018: PDUFA date for Makena subcutaneous auto-injector; prepare for first quarter 2018 potential approval and subsequent launch;
•
First quarter 2018: submit bremelanotide new drug application to FDA;
•
Continue to broaden awareness and drive prescriptions of Intrarosa
‒
Increase formulary coverage (65% unrestricted commercial lives covered anticipated by month end);
‒
Increase the number of healthcare professional prescribers (from ~4,200 achieved in 2017);
‒
Increase the number of total prescriptions written (from ~20,000 in 2017);
‒
Increase market share (from year-end weekly NRx share of 2.6%);
‒
Launch digital-to-direct consumer campaign in first half of 2018;
•
Expand CBR first time enrollments; and
•
Further diversify product portfolio through disciplined business development.

"In 2017, we delivered strong top-line and adjusted EBITDA results while investing aggressively in the products that will drive our future growth. We also improved our liability profile so that our balance sheet is better aligned with our evolving business strategy. Finally, we have managed and will continue to manage our expenses carefully to maintain operational flexibility," said Ted Myles, AMAG’s chief financial officer. "​We are guiding to continued positive adjusted EBITDA generation​ in 2018, and with $329 million of cash on hand as of December 31, 2017, ​we are in a strong position to continue to invest in our current products, while remaining active in the search for additional asset acquisitions or licensing transactions that provide durable, long-term growth."

Webcast Information
A live audio webcast of the company’s presentation and the following breakout session, along with the accompanying slide presentation at the 36th Annual J.P. Morgan Healthcare Conference, will be accessible through the Investors section of the company’s website at www.amagpharma.com on January 9, 2018 at 10:00 a.m. P.T. (1:00 p.m. E.T.). Following the conference, the webcast will be archived on the company’s website until February 9, 2018.

Use of Non-GAAP Financial Measures
AMAG has presented certain non-GAAP financial measures, including non-GAAP revenue and non-GAAP adjusted EBITDA (earnings before income taxes, depreciation and amortization). These non-GAAP financial measures exclude certain amounts, revenue, expenses or income, from the corresponding financial measures determined in accordance with accounting principles generally accepted in the U.S. (GAAP). Management believes this non-GAAP information is useful for investors, taken in conjunction with AMAG’s GAAP financial statements, because it provides greater transparency regarding AMAG’s operating performance. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of AMAG’s operating results as reported under GAAP, not as a substitute for GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures are included in the tables at the conclusion of this press release.

On January 7, 2018 Shanghai Sinobioway Sunterra Biotechnology (SSSB) and F1 Oncology reported the signing of new development, manufacturing, and supply agreements with plans to complete a new cGMP manufacturing facility in Shenzhen in support of large scale lentivirus contract manufacturing (Press release, EXUMA Biotechnology, JAN 7, 2018, View Source [SID1234619679]). The new facility, Shenzhen Biowit, which will expand from the current clinical production staff and site in Shenzhen, is scheduled for completion in 2018 and will utilize F1 Oncology’s chemically defined suspension-based lentivirus manufacturing technology and processes. The Shenzhen Biowit facility, in collaboration with F1 Oncology’s Hong Kong affiliate, will support future China gene therapy markets with clinical and commercial cGMP lentivirus for CAR-T and other gene therapies.

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The new collaboration agreements between F1 Oncology’s international affiliates and Sinobioway Sunterra Biotechnology will facilitate clinical development and commercialization of F1 Oncology’s CCT3-based conditionally active biologic chimeric antigen receptor T cell (CAB-CAR-T) products in China, Hong Kong, Macau, and Taiwan. F1 Oncology retains rights to CCT3 products in all other territories and exclusive responsibility for global manufacturing and supply of certain product classes.

Upon SSSB’s closing of certain financing activities, SSSB will issue to F1 Oncology 20% equity plus 5% warrants. F1 Oncology will be responsible for lead generation, preclinical safety assessment and clinical virus manufacturing costs. Sinobioway Sunterra Biotechnology will be responsible for cGMP cell processing, clinical development, regulatory approval, and commercialization in the defined territories.

The agreement provides for certain licensing fees to be paid by SSSB upon nomination of new CAR-T products with preclinical packages delivered to SSSB for commercialization. The agreement further provides for processing of raw materials provided by F1 Oncology’s international affiliates and production to supply commercial products to the China markets.

"Biowit, a subsidiary of SSSB, has been providing the majority of cell therapy research institutions in China with virus products service over the past 7 years. Today, the introduction of F1 Oncology’s chemically defined suspension-based lentivirus manufacturing technology marks a new stage of China clinical virus manufacturing. Through our one year-old collaboration, Sunterra is leveraging the value of F1 Oncology’s CAB-CAR-T technology and proprietary industrial manufacturing processes to begin novel CAR-T clinical trials in China. We are confident that F1 Oncology’s differentiating technologies will allow us to stand out from other players in the CAR-T solid tumor space." Stated Mr. Wu Zili, Board Director and founder of SSSB.

"Reliable supply of viral gene vectors for cell and gene therapy programs is a current and growing challenge for the commercial biotechnology industry, and generally requires a different facility configuration to those used for traditional biologics" stated Tim Mayall, Ph.D. Head of Process Development at F1 Oncology. "Our early investments in the generation of serum-free well-characterized cell substrates capable of suspension-based lentivirus production supports a scalability that we believe will be beneficial from first in human through commercialization."

On January 7, 2018 Neurocrine Biosciences, Inc. (NASDAQ: NBIX), a biotechnology company focused on neurological and endocrine related disorders, reported that Christopher O’Brien, M.D., Chief Medical Officer, has notified the Company he plans to retire in February 2018, after a transition period with his successor (Press release, Neurocrine Biosciences, JAN 7, 2018, View Source;p=RssLanding&cat=news&id=2325239 [SID1234522940]). Dr. O’Brien joined Neurocrine in 2005, and has led the clinical development and medical affairs activities for more than 12 years. Dr. O’Brien will remain as an exclusive consultant for Neurocrine.

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"On behalf of the board, shareholders and our employees, I want to thank Chris for his tremendous contributions as Chief Medical Officer of Neurocrine," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "With his considerable expertise and leadership, we successfully developed and obtained FDA approval of INGREZZA capsules for the treatment of adults with tardive dyskinesia and advanced our clinical development programs for Tourette syndrome, Parkinson’s disease, endometriosis and congenital adrenal hyperplasia. I am very pleased that Chris will continue to be a part of the Neurocrine team for the foreseeable future."

Eiry W. Roberts, M.D., will join the company as Chief Medical Officer, effective January 8, 2018.

"We are very pleased to welcome Eiry to Neurocrine as she brings extensive senior leadership and pharmaceutical management experience to the team," Dr. Gorman said. "Eiry’s strong background in implementing strategic clinical development programs and navigating the regulatory approvals process across phases of drug development from research to commercialization in multiple therapeutic areas, including neuroscience, will be valuable as we execute on our commercialization and clinical plans and advance our pipeline in support of our commitment to relieve patient suffering and enhance lives."

Dr. Roberts has over 25 years of research and development experience in the pharmaceutical industry across all phases of drug development from research through commercialization in multiple therapeutic areas, including neuroscience, inflammation, oncology and metabolic diseases. She joins Neurocrine from Eli Lilly and Company where she held various positions during her tenure, including Vice President, Clinical Pharmacology and Vice President of R&D, BioMedicines Business Unit.

Dr. Roberts was the Chair of the Medical Review Committee, where she was responsible for review and approval of all the integrated clinical plans for molecules in the Lilly portfolio. She was also a member of Lilly’s Corporate Portfolio Management Committee and Lilly Ventures Steering Committee. Dr. Roberts was accountable for early clinical development programs across all therapeutic areas within Lilly, as well as registration for new chemical entities and biproducts in Phase III development. During her time at Lilly, Dr. Roberts established a new therapeutic area, which resulted in the development of five potential novel medicines from Phase I through to approval, with two of them successfully receiving regulatory approval. Dr. Roberts also has extensive leadership and business development experience, including the management of strategic alliances, business partnerships and venture capital collaborations.

Dr. Roberts is a physician who trained in pharmacology and medicine in the UK, qualifying from the University of London in 1987. Her post-graduate clinical training was in clinical pharmacology and cardiology at St. Bartholomew’s Hospital and the Royal London Hospital.

Neurocrine also announced the grant of an inducement award to Dr. Roberts pursuant to Rule 5635(c)(4) of the NASDAQ Listing Rules. In connection with her employment by Neurocrine, Dr. Roberts will be granted an inducement award consisting of a stock option to purchase 70,000 shares of Neurocrine common stock. The stock option will vest over a period of four years, with 25% vesting on the first anniversary of its grant date and the balance vesting each month over the remaining three years. Dr. Roberts also received 20,000 restricted stock units which vest in equal increments over four years, with 25% vesting each year. These awards are subject to the terms and conditions of Neurocrine’s Inducement Plan, and will be effective on January 8, 2018. The stock option grant will have an exercise price equal to the closing price of Neurocrine’s common stock on the NASDAQ Global Select Market on that date. These awards were granted as an inducement material to Dr. Roberts’ employment pursuant to Rule 5635(c)(4) of the NASDAQ Listing Rules.

On January 7, 2018 Celgene Corporation (NASDAQ:CELG) and Impact Biomedicines reported the signing of a definitive agreement in which Celgene will acquire Impact Biomedicines, which is developing fedratinib for myelofibrosis and polycythemia vera (Press release, Celgene, JAN 7, 2018, View Source [SID1234522934]). Under the terms of the agreement, Celgene will pay approximately $1.1 billion upfront and up to $1.25 billion in contingent payments based on regulatory approval milestones for myelofibrosis. Additional future payments for regulatory approvals in additional indications and sales-based milestones are also possible.

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Fedratinib, a highly selective JAK2 kinase inhibitor, was evaluated in 877 patients across 18 clinical trials. In a randomized, placebo-controlled, phase III pivotal trial (JAKARTA-1) for patients with treatment-naïve myelofibrosis, fedratinib demonstrated statistically significant improvements in the primary and secondary endpoints of splenic response and total symptom score, respectively. In an exploratory subgroup analysis, these improvements were observed regardless of a patient’s baseline platelet count.

A multi-center, single-arm phase II trial (JAKARTA-2) evaluated fedratinib in myelofibrosis patients who were found to be resistant or intolerant to ruxolitinib (Jakafi), a JAK1/JAK2 inhibitor. In this second-line setting, fedratinib demonstrated clinically meaningful improvements in splenic response and total symptom score.

As previously reported, JAKARTA-2 was stopped prematurely due to a clinical hold placed on the fedratinib program by the U.S. Food and Drug Administration (FDA) after potential cases of Wernicke’s encephalopathy (WE) were reported in eight out of 877 patients receiving one or more doses (less than one percent of treated patients). The FDA removed the clinical hold in August 2017.

Based on the reported benefit risk profile of fedratinib from the JAKARTA-1 and JAKARTA-2 clinical trials, regulatory applications in myelofibrosis are planned beginning in the middle of 2018.

"Myelofibrosis is a disease with high unmet medical need as the number of patients who are ineligible for or become resistant to existing therapy continues to increase," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "We believe fedratinib is uniquely positioned as a potential treatment for myelofibrosis and it provides strategic options for us to build leadership in this disease with luspatercept and other pipeline assets."

"We launched Impact Biomedicines and based on our thorough review of the data, fedratinib presents a compelling risk benefit profile in both treatment-naïve patients and patients who are resistant or intolerant to other JAK2 therapies," said Dr. John Hood, Chief Executive Officer of Impact. "We believe Celgene is the ideal organization to follow through on our mission of maximizing fedratinib’s potential for patients with myelofibrosis."

Deal Terms

Under the terms of the agreement, Celgene will make an upfront cash payment of approximately $1.1 billion. In addition, Impact Biomedicines’ shareholders are eligible to receive contingent payments based on regulatory approval and sales-based milestones. The maximum aggregate amount payable for regulatory approval milestones is $1.4 billion relating to approvals for myelofibrosis and other indications. Starting from global annual net sales of $1.0 billion, aggregate tiered sales-based milestone payments could total a maximum of $4.5 billion if global annual net sales exceed $5.0 billion.

Credit Suisse acted as financial advisor and Hogan Lovells acted as legal counsel to Celgene on the transaction. PJT Partners acted as exclusive financial advisor and Latham & Watkins acted as exclusive legal counsel to Impact Biomedicines on the transaction. The acquisition is subject to customary closing conditions and applicable waiting period under the Hart Scott Rodino Antitrust Improvements Act. The transaction is expected to close in the first quarter of 2018.