Five Prime Therapeutics Earns IND Milestone Payment Under Immune Checkpoint Pathways Discovery Collaboration with Bristol-Myers Squibb and Announces that BMS has Extended the Research Term of this Collaboration for a Second Time

On January 8, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that it has achieved a milestone for the first Investigational New Drug (IND) application to the U.S. Food and Drug Administration by Bristol-Myers Squibb Company (BMS) (NYSE:BMY) for a therapeutic candidate under the immune checkpoint pathway discovery collaboration between the companies (Press release, Five Prime Therapeutics, JAN 8, 2018, View Source [SID1234522980]). The first clinical candidate from the collaboration is a fully-human monoclonal antibody targeting TIM-3 (T-cell immunoglobulin and mucin domain-3), an immune checkpoint receptor that is known to limit the duration and magnitude of T-cell responses1. This first IND application triggers a $5 million milestone payment to Five Prime.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to see Bristol-Myers Squibb file an IND for the first innovative immuno-oncology therapeutic candidate to advance to the clinic under our immuno-oncology discovery collaboration," said Bryan Irving, Ph.D. Senior Vice President, Research at Five Prime. "TIM-3 is thought to inhibit the response of T cells and other crucial immune cell types, so blocking this checkpoint pathway could be a promising component of an immuno-oncology strategy to treat a variety of tumors."

Under the terms of the discovery collaboration agreement, BMS has exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets in three checkpoint pathways. Five Prime is eligible to receive up to $300 million in future development, regulatory and sales-based milestone payments for each collaboration target, including TIM-3. Five Prime is also eligible to receive tiered royalties starting from mid-single-digit increasing to low-double-digit percentages of global net sales of each product commercialized by BMS.

In addition, BMS has exercised its option to further extend the research term of the collaboration between the companies for the discovery, development and commercialization of immuno-oncology (I-O) therapies directed toward targets in two additional undisclosed immune checkpoint pathways. BMS has elected to extend the research term to March 2019 and will provide additional funding to Five Prime for the extended term. This is the second extension to the original collaboration term under the agreement that was established in March 2014.

BMS will continue to utilize Five Prime’s discovery capabilities to advance the immune checkpoint programs, including to identify and select drug candidates for preclinical development. Drug candidates developed against targets in these pathways may be studied either as single agents or in combination with approved BMS immuno-oncology therapies or others in development.

Corporate Presentation

On January 8, 2018 Karyopharm presented Corporate Presentation current as of January 8, 2018 (Presentation, Karyopharm, JAN 8, 2018, View Source [SID1234522975]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Adaptimmune Announces Positive Safety Data from Pilot Studies with MAGE-A10 SPEAR T-cells and First Patient to Receive 1 billion Target Cell Dose

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.

AMAG Pharmaceuticals Announces Preliminary 2017 Financial Results
and Provides 2018 Guidance

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Oncoceutics Extends IP Coverage to Japan with New Patent Covering All Cancers

On January 8, 2018 Oncoceutics, Inc. reported that the Japanese Patent Office (JPO) has issued Japanese Patent No. 6132833 for the use of ONC201 to treat all cancers or patients having a risk of cancer, including brain, colon, breast, colorectal cancers, and glioblastoma (Press release, Oncoceutics, JAN 8, 2018, https://oncoceutics.com/oncoceutics-extends-ip-coverage-japan-new-patent-covering-cancers/ [SID1234558374]). The claims issued also include the use of ONC201 when administered in conjunction with another anticancer agent and 25 routes of administration, including oral administration.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This is the first patent issued outside the United States covering ONC201. This patent, combined with issued patents for ONC201 formulation and use in combination with other therapies, as well as FDA regulatory designations that ONC201 has received, provides ONC201 with a robust suite of intellectual property.

ONC201, a member of the imipridone family, has demonstrated anti-cancer activity and safety in preclinical models and ongoing clinical trials, including a trial for various solid and liquid tumors. Oncoceutics has also received patents covering its next generation of imipridones, namely ONC206 and ONC212.

"We are delighted that the Japanese Patent Office has recognized these indications as novel uses of ONC201 and granted these broad patent protections in such an important market," said Martin Stogniew, Ph.D., Chief Development Officer of Oncoceutics. "The company’s current patent estate gives Oncoceutics more than 15 years of patent protection for the vast majority of human cancers, including tumor types where ONC201 is currently in Phase II trials."