On October 27, 2017 Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) (“Eagle” or “the Company”) reported that the United States Food and Drug Administration (“FDA”) has granted tentative approval for the Company’s PEMFEXY, a pemetrexed injection ready-to-dilute formulation for locally advanced or metastatic nonsquamous non-small cell lung cancer in combination with cisplatin; locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy, as maintenance treatment; locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy as a single agent; and malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery in combination with cisplatin (Press release, Eagle Pharmaceuticals, OCT 27, 2017, View Source [SID1234521256]).

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“We are pleased to have received this tentative approval for PEMFEXY, which we believe offers a material benefit to healthcare providers. PEMFEXY fits well within our growing portfolio of oncology drugs, including BENDEKA, bendamustine hydrochloride ready-to-dilute and rapid infusion, DOCETAXEL INJECTION, and fulvestrant, which is in development. We will work toward bringing this much needed drug to market as soon as the patent issues are resolved,” stated Scott Tarriff, Chief Executive Officer.

“Tentative approval” means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, but is not eligible for marketing in the U.S. because of existing patent protections. The tentative approval will be eligible for conversion to a final approval subject to the resolution of the current patent litigation between Eagle and Eli Lilly and Co.

“Our formulation does not require reconstitution, reducing the potential for dosing errors during mixing as well as the hazards of inhaling cytotoxic vapors that can occur when handling the powder form of the drug during preparation. We believe there is a need in the market for our improved formulation,” concluded Tarriff.

Eagle submitted, and the FDA accepted for filing, its NDA under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“FDCA”) for PEMFEXY ready-to-dilute in December 2016.

This NDA references ALIMTA, the branded product manufactured by Eli Lilly and Co., which had annual U.S. sales of approximately $1.0 billion over the last twelve months.

On October 27, 2017 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported financial results for the third quarter of 2017 (Press release, Merck & Co, OCT 27, 2017, View Source [SID1234521238]).

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"Our performance in the third quarter demonstrates the strength of our underlying business, with growth from key product launches, good global demand for vaccines, as well as strength from our Animal Health business," said Kenneth C. Frazier, chairman and chief executive officer, Merck. "We will continue augmenting our pipeline through value-creating business development like our oncology collaboration with AstraZeneca to address unmet medical need and drive future growth."

Financial Summary

Third Quarter
$ in millions, except EPS amounts 2017 2016
Sales $10,325 $10,536
GAAP net (loss) income1
(56) 2,184
Non-GAAP net income that excludes items listed below1,2
3,054 2,989
GAAP EPS (0.02) 0.78
Non-GAAP EPS that excludes items listed below2
1.11 1.07

Worldwide sales were $10.3 billion for the third quarter of 2017, a decrease of 2 percent compared with the third quarter of 2016, including a 1 percent positive impact from foreign exchange.

Sales in the third quarter of 2017 were reduced by approximately $240 million due to a borrowing from the U.S. Centers for Disease Control and Prevention Pediatric Vaccine Stockpile of GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant), a vaccine to prevent certain cancers and other diseases caused by HPV, driven in part by the temporary production shutdown resulting from the cyber-attack, as well as overall higher demand than originally planned.

Additionally, as expected, revenue was unfavorably impacted by approximately $135 million from lost sales in certain markets related to the cyber-attack. Sales in the third quarter of 2017 compared with the third quarter of 2016 were also unfavorably impacted by approximately $150 million of additional sales in Japan in the third quarter of 2016 resulting from the timing of shipments. Sales in the third quarter of 2017 reflect incremental sales of approximately $130 million due to the recording of vaccine sales from 19 European countries that were part of the Sanofi Pasteur MSD (SPMSD) vaccines joint venture, which was terminated on Dec. 31, 2016.

GAAP (generally accepted accounting principles) earnings (loss) per share assuming dilution (EPS) were $(0.02) for the third quarter of 2017, which reflects a $2.35 billion aggregate charge related to the formation of a strategic oncology collaboration with AstraZeneca. Non-GAAP EPS of $1.11 for the third quarter of 2017 excludes acquisition- and divestiture-related costs, restructuring costs, the charge related to the AstraZeneca collaboration referenced above and certain other items. Year-to-date results can be found in the attached tables.

Pipeline Highlights

Merck expanded its focus in oncology by further advancing the development program for KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, receiving key regulatory approvals and through business development transactions.

The U.S. Food and Drug Administration (FDA) approved KEYTRUDA under its Accelerated Approval program for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 and who have already received two or more lines of chemotherapy.
The European Commission approved KEYTRUDA for the treatment of certain patients with locally advanced or metastatic urothelial carcinoma.
At the European Society for Medical Oncology 2017 Congress, data were presented from studies evaluating the use of KEYTRUDA as a monotherapy and combination therapy in 12 cancers.
Merck is amending the KEYNOTE-189 study to include overall survival as a co-primary endpoint. The updated completion date is Feb. 2019 and there will be opportunities for the company to conduct interim analyses. KEYNOTE-189 is a Phase 3 study of platinum-pemetrexed chemotherapy with or without KEYTRUDA in patients with first line metastatic non-squamous non-small cell lung cancer (NSCLC).
Merck entered into an oncology collaboration with AstraZeneca to co-develop and co-commercialize AstraZeneca’s Lynparza (olaparib), a PARP inhibitor, and investigational medicine selumetinib, a MEK inhibitor, as monotherapy and in combination treatments for multiple cancer types.
The FDA approved Lynparza for new and additional uses in ovarian cancer, including as a maintenance treatment for recurrent epithelial ovarian, fallopian tube or primary peritoneal adult cancer patients who are in response to platinum-based chemotherapy, regardless of BRCA status, and in tablets for the use in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy.
The FDA accepted for review the supplemental New Drug Application (NDA) for the use of Lynparza tablets in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer who have been previously treated with chemotherapy either in the neoadjuvant, adjuvant or metastatic settings. The FDA granted Priority Review with a PDUFA action date in the first quarter of 2018. A NDA was also submitted to Japan’s Pharmaceuticals and Medical Devices Agency.
Merck acquired Rigontec, a pioneer in accessing the retinoic acid-inducible gene I (RIG-I) pathway, part of the innate immune system, as a novel and distinct approach in cancer immunotherapy to induce both immediate and long-term anti-tumor immunity. Rigontec’s lead candidate, RGT100, is currently in Phase I development evaluating treatment in patients with various tumors. The acquisition closed in October.
Merck presented results at the European Research Organization on Genital Infection and Neoplasia Congress from the final analyses of the pivotal Phase 3 efficacy, immunogenicity and safety clinical trial for GARDASIL 9 showing sustained efficacy for up to six years in the per protocol population.

Merck presented data at ID Week 2017 from the pivotal Phase 3 clinical study of letermovir, an investigational antiviral medicine for prophylaxis of cytomegalovirus (CMV) infection or disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant. Data were also presented from the Phase 1 trial for V160, an investigational vaccine for human CMV, evaluating safety, tolerability and immunogenicity in healthy adults.

Merck announced it will not submit applications for regulatory approval for anacetrapib, the investigational cholesteryl ester transfer protein inhibitor, following a thorough review of the clinical profile of anacetrapib, including discussions with external experts.

Merck announced the strategic decision to discontinue the development of the investigational combination regimens MK-3682B (grazoprevir/ruzasvir/uprifosbuvir) and MK-3682C (ruzasvir/uprifosbuvir) for the treatment of chronic hepatitis C virus (HCV) infection. This decision was made based on a review of available Phase 2 efficacy data and in consideration of the evolving marketplace and the growing number of treatment options available for patients with chronic HCV infection, including ZEPATIER (elbasvir and grazoprevir).

Third-Quarter Revenue Performance

The following table reflects sales of the company’s top pharmaceutical products, as well as total sales of Animal Health products.

$ in millions Third Quarter
2017 2016 Change
Change
Ex-Exchange
Total Sales $10,325 $10,536 -2% -3%
Pharmaceutical 9,156 9,443 -3% -4%
JANUVIA / JANUMET 1,525 1,554 -2% -2%
KEYTRUDA 1,047 356 194% 192%
GARDASIL / GARDASIL 9 675 860 -22% -22%
PROQUAD,
M-M-R II and VARIVAX
519 496 4% 5%
ZEPATIER 468 164 185% 184%
ZETIA / VYTORIN 462 944 -51% -52%
ISENTRESS / ISENTRESS HD 310 372 -17% -18%
ZOSTAVAX 234 190 23% 23%
PNEUMOVAX 23 229 175 31% 31%
Animal Health 1,000 865 16% 14%
Other Revenues 169 228 -26% -13%

Pharmaceutical Revenue

Third-quarter pharmaceutical sales decreased 3 percent to $9.2 billion, including a 1 percent positive impact from foreign exchange. In addition to the factors mentioned in the Financial Summary above, sales in the third quarter of 2017 reflect the loss of market exclusivity for several products, as well as lower sales of JANUVIA (sitagliptin) and JANUMET (sitagliptin and metformin HCl), medicines that help lower blood sugar in adults with type 2 diabetes. These declines were partially offset by significant growth in KEYTRUDA and from other product launches, as well as from growth in certain in-line brands.

The pharmaceutical sales decline was largely driven by the loss of U.S. market exclusivity for ZETIA (ezetimibe) in late 2016 and VYTORIN (ezetimibe/simvastatin) in April 2017, medicines for lowering LDL cholesterol, and the ongoing impacts of generic competition for CUBICIN (daptomycin for injection), an I.V. antibiotic, and biosimilar competition for REMICADE (infliximab), a treatment for inflammatory diseases, in the company’s marketing territories in Europe. In the aggregate, sales of these products declined approximately $800 million during the third quarter of 2017 compared to the third quarter of 2016.

Additionally, the decline reflects lower sales of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] and GARDASIL 9, vaccines to prevent certain cancers and other diseases caused by HPV, largely attributable to lower sales in the United States as described previously, partially offset by growth in Europe due to the termination of the SPMSD vaccines joint venture noted above, and growth in Asia Pacific reflecting strong demand.

The decrease in the diabetes franchise of JANUVIA and JANUMET was primarily due to pricing pressure partially offset by continued volume growth globally.

Higher sales of KEYTRUDA reflect the company’s continued launch with new indications globally. Strong momentum from the treatment of patients with NSCLC contributed significantly to KEYTRUDA’s overall growth, as KEYTRUDA is the only anti-PD-1 approved in the first-line setting.

Growth in ZEPATIER is due to ongoing launches globally. The company anticipates that future sales of ZEPATIER will be unfavorably affected by increasing competition and declining patient volumes.

Additionally, the ongoing launch of BRIDION (sugammadex) Injection 100 mg/mL, a medicine for the reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide in adults undergoing surgery, generated sales of $185 million in the quarter driven largely by strong growth in the United States.

Growth in PNEUMOVAX 23 (pneumococcal vaccine polyvalent), a vaccine to help prevent pneumococcal disease, was largely due to higher demand and pricing in the United States.

Animal Health Revenue

Animal Health sales totaled $1.0 billion for the third quarter of 2017, an increase of 16 percent compared with the third quarter of 2016, including a 2 percent positive impact from foreign exchange. Growth was driven by sales increases in companion animal products, primarily the BRAVECTO (fluralaner) line of products that kill fleas and ticks in dogs and cats for up to 12 weeks, and companion animal vaccines. Additionally, higher sales of ruminants products, including the positive impact of the Vallée S.A. acquisition which closed in March, swine products and poultry products all contributed to growth.

Third-Quarter Expense, EPS and Related Information

The table below presents selected expense information.

$ in millions
Third-Quarter 2017

GAAP

Acquisition- and
Divestiture-
Related Costs 3

Restructuring
Costs

Certain Other
Items

Non-GAAP 2
Materials and production $3,274 $768 $25 $– $2,481
Marketing and administrative 2,401 11 – – 2,390
Research and development 4,383 271 2 2,350 1,760
Restructuring costs 153 – 153 – –
Other (income) expense, net (86) (18) – – (68)

Third-Quarter 2016
Materials and production $3,409 $773 $36 $– $2,600
Marketing and administrative 2,393 36 1 – 2,356
Research and development 1,664 13 14 – 1,637
Restructuring costs 161 – 161 – –
Other (income) expense, net 22 12 – (6) 16

GAAP Expense, EPS and Related Information

On a GAAP basis, the gross margin was 68.3 percent for the third quarter of 2017 compared to 67.6 percent for the third quarter of 2016. The increase in gross margin for the third quarter of 2017 was primarily driven by the favorable effects of product mix partially offset by costs related to the cyber-attack.

Marketing and administrative expenses were $2.4 billion in the third quarter of 2017, essentially flat as compared to the third quarter of 2016. Lower acquisition- and divestiture-related costs were offset by costs associated with the company now operating its European vaccines business in the countries that were previously part of the SPMSD vaccines joint venture, higher promotion expenses related to product launches and remediation costs related to the cyber-attack.

Research and development (R&D) expenses were $4.4 billion in the third quarter of 2017 compared with $1.7 billion in the third quarter of 2016. The increase primarily reflects a $2.35 billion aggregate charge related to the formation of the collaboration with AstraZeneca, higher in-process research and development (IPR&D) impairment charges driven by a $240 million charge resulting from the decision to discontinue the development of investigational HCV combination regimens MK-3682B and MK-3682C noted above, and increased investment in early drug development.

The GAAP effective income tax rate of 125.5 percent for the third quarter of 2017 reflects the unfavorable impact of a $2.35 billion aggregate charge related to the formation of the AstraZeneca collaboration for which no tax benefit has been recognized, partially offset by the favorable impact of a net tax benefit of $234 million related to the settlement of certain federal income tax issues.

GAAP EPS was $(0.02) for the third quarter of 2017 compared with $0.78 for the third quarter of 2016.

Non-GAAP Expense, EPS and Related Information

The non-GAAP gross margin was 76.0 percent for the third quarter of 2017 compared to 75.3 percent for the third quarter of 2016. The increase in non-GAAP gross margin was largely driven by the favorable effects of product mix partially offset by costs related to the cyber-attack.

Non-GAAP marketing and administrative expenses were $2.4 billion in the third quarter of 2017, an increase of 1 percent compared to the third quarter of 2016. The increase in non-GAAP marketing and administrative expenses was driven primarily by costs associated with the company now operating its European vaccines business in the countries that were previously part of the SPMSD vaccines joint venture, higher promotion expenses related to product launches and remediation costs related to the cyber-attack.

Non-GAAP R&D expenses were $1.8 billion in the third quarter of 2017, an 8 percent increase compared to the third quarter of 2016. The increase reflects increased investment in early drug development.

The non-GAAP effective income tax rate was 18.7 percent compared to 23.8 percent in the third quarter of 2016.

Non-GAAP EPS was $1.11 for the third quarter of 2017 compared with $1.07 for the third quarter of 2016.

A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that follows.

$ in millions, except EPS amounts Third Quarter
2017 2016
EPS
GAAP EPS $(0.02) $0.78
Difference4
1.13 0.29
Non-GAAP EPS that excludes items listed below2 $1.11 $1.07

Net Income
GAAP net (loss) income1 $(56) $2,184
Difference 3,110 805
Non-GAAP net income that excludes items listed below1,2 $3,054 $2,989

Decrease (Increase) in Net Income Due to Excluded Items:
Acquisition- and divestiture-related costs3 $1,032 $834
Restructuring costs 180 212
Aggregate charge related to the formation of the collaboration with AstraZeneca 2,350 –
Other – (6)
Net decrease (increase) in income before taxes 3,562 1,040
Income tax (benefit) expense5
(452) (235)
Decrease (increase) in net income $3,110 $805

Financial Outlook

Merck has narrowed and raised its full-year 2017 GAAP EPS range to be between $1.78 and $1.84. Merck narrowed and raised its full-year 2017 non-GAAP EPS range to be between $3.91 and $3.97, including a less than 1 percent negative impact from foreign exchange at current exchange rates. The non-GAAP range excludes acquisition- and divestiture-related costs, costs related to restructuring programs, a charge related to the formation of the collaboration with AstraZeneca and certain other items.

Merck has narrowed and raised its full-year 2017 revenue range to be between $40.0 billion and $40.5 billion, including a less than 1 percent negative impact from foreign exchange at current exchange rates.

The following table summarizes the company’s 2017 financial guidance.

GAAP Non-GAAP 2

Revenue $40.0 to $40.5 billion
$40.0 to $40.5 billion*
Operating expenses Lower than 2016 Higher than 2016 by a mid-single digit rate
Effective tax rate 24.5% to 25.5% 20.0% to 21.0%
EPS $1.78 to $1.84 $3.91 to $3.97
*The company does not have any non-GAAP adjustments to revenue.

A reconciliation of anticipated 2017 GAAP EPS to non-GAAP EPS and the items excluded from non-GAAP EPS are provided in the table below.

$ in millions, except EPS amounts

Full-Year 2017

GAAP EPS $1.78 to $1.84
Difference4 2.13
Non-GAAP EPS that excludes items listed below2 $3.91 to $3.97

Acquisition- and divestiture-related costs $3,800
Restructuring costs 850
Aggregate charge related to the formation of the collaboration with AstraZeneca 2,350
Net decrease (increase) in income before taxes 7,000
Estimated income tax (benefit) expense (1,130)
Decrease (increase) in net income $5,870

The expected full-year 2017 GAAP effective tax rate of 24.5 to 25.5 percent reflects an unfavorable impact of approximately 4.5 percentage points from the above items.

Total Employees

As of Sept. 30, 2017, Merck had approximately 69,500 employees worldwide.

On October 26, 2017 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported financial results for the third quarter ended September 30, 2017 (Press release, BioMarin, OCT 26, 2017, View Source [SID1234521209]).

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For the quarter ended September 30, 2017, GAAP Net Loss was $(12.5) million, or $(0.07) per basic and diluted share, compared to GAAP Net Loss of $(37.4) million, or $(0.22) per basic and diluted share for the quarter ended September 30, 2016. The reduction in GAAP Net Loss year over year was primarily due to the $31.5 million net upfront license payment received as a result of the License and Settlement Agreements entered into with Sarepta Therapeutics Inc. in July 2017. The decreased GAAP Net Loss was also driven by increased net product revenues for Kuvan and Vimizim, partially offset by a decrease in the Benefit From Income Taxes, and increased Selling, General and Administrative expenses for Kuvan, Brineura and Vimizim. BioMarin also announced today that full year GAAP net loss guidance is being reduced to between ($110) million and ($130) million.

Non-GAAP Income for the third quarter ended September 30, 2017 was $7.8 million, compared to Non-GAAP Income of $2.9 million for the quarter ended September 30, 2016. BioMarin also announced today that full year Non-GAAP Income guidance is being increased to between $60 million and $80 million.

Total Revenues were $334.1 million for the third quarter of 2017, and were $955.3 million for the nine months ended September 30, 2017, an increase of 19% and 17% respectively compared to the same periods in 2016. For the nine months ended September 30, 2017, Kuvan net product revenues increased 16% year over year. Growth was driven by a 9% increase in the number of commercial patients on Kuvan therapy in the U.S and the continued growth in the ex-North American territories acquired in 2016. For the nine months ended September 30, 2017, Naglazyme net product revenues increased by 8% year over year, due primarily to an increase of 7% in the number of Naglazyme commercial patients. Vimizim net product revenues increased 15% year over year during the nine months ended September 30, 2017. The number of Vimizim commercial patients increased 23% year over year.

On October 18, 2017, the Company commented on its Total Revenue and Non-GAAP Income (Loss) trends for the third quarter and full-year 2017. In terms of the overall commercial business, BioMarin stated that sales of products in markets throughout most of the world are performing at or above internal expectations. However, the Company said the one exception is Brazil, where a slowdown in federal purchasing orders had extended into the third quarter of this year. As a result, third quarter revenues were negatively impacted. Since October 18, the Brazilian Ministry of Health has initiated their purchasing process which is expected to result in net product revenue from Brazil in the fourth quarter. Based on this order Total Revenues for full-year 2017 are confirmed to be within prior guidance.

As of September 30, 2017, BioMarin had cash, cash equivalents and investments totaling approximately $1.7 billion, as compared to $1.4 billion on December 31, 2016.

Commenting on the quarter, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, “We achieved a number of important strategic milestones so far this year, including record Total Revenues in the third quarter and the go ahead from both U.S. and U.K. health authorities to begin Phase 3 studies with valoctocogene roxaparvovec (formerly referred to as BMN 270) gene therapy program for severe hemophilia A by year-end.” Mr. Bienaimé continued, “We had many significant updates at our recent R&D Day, including the announcement of our next IND candidate BMN 290 for Freidriech’s Ataxia, a rare neurologic disorder that affects nearly 15,000 people worldwide. We were also pleased to share that vosoritide for achondroplasia demonstrated a sustained increase in annualized growth rate at 30 months of treatment. For pegvaliase, we anticipate FDA action on our Biologics License Application in the first half of 2018, as well as our planned submission of the Marketing Authorization Application in Europe in the first quarter of 2018. With these programs all advancing, supported by our strong base commercial business, we have reduced our GAAP Net Loss guidance and increased our Non-GAAP Income guidance for the full-year 2017.”

Key Program Updates at R&D Day October 18, 2017

BMN 290 for Freidriech’s Ataxia (FA): BioMarin announced that it has selected as its next drug development candidate, BMN 290, a selective chromatin modulation therapy intended for treatment of FA. FA is a rare autosomal recessive disorder with worldwide prevalence of approximately 15,000, which results in disabling neurologic and cardiac progressive decline. Currently there are no approved disease modifying therapies for FA. In preclinical models, BMN 290 increases frataxin expression in affected tissues more than two-fold. BMN 290 is a second-generation compound derived from a compound the Company acquired from Repligen Corporation (Repligen) that had human clinical data demonstrating increases in frataxin in FA patients. The Company selected BMN 290 for its favorable penetration into the central nervous system and cardiac target tissues, and its preservation of the selectivity of the original Repligen compound. The Company expects to submit the IND application for BMN 290 in the second half of 2018.

Valoctocogene roxaparvovec (formerly referred to as BMN 270) gene therapy for hemophilia A: BioMarin announced today that it had been granted Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for valoctocogene roxaparvovec. The designation is intended to expedite the development and review of medicines to treat a serious disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. The Company also announced that the 6e13 vg/kg dose and 4e13 vg/kg dose had been cleared by both U.S. and U.K. health authorities to begin Phase 3 studies.

The protocol for each Phase 3 study, one using the 6e13 vg/kg dose and one using the 4e13 vg/kg dose, will likely include approximately 40 patients for a duration of 52 weeks per study. The Company expects to file for approval of valoctocogene roxaparvovec with 52-week data from the Phase 3 studies. BioMarin expects to initiate the global Phase 3 program in the fourth quarter of 2017, complete enrollment of the last patient by the end of 2018 and provide top-line Phase 3 data by the end of 2019.

At R&D Day, the Company provided an update on the ongoing open-label Phase 1/2 study of the 4e13 vg/kg dose at up to 36 weeks of observation at the September 14, 2017 data cut. Since the last data update provided during the second quarter earnings call on August 2, 2017, five of the six patients at the 4e13 vg/kg dose tracked to the low range of normal, and the sixth is in the mild range for Factor VIII levels. Median annualized bleed and factor VIII use rates for 4e13 and 6e13 vg/kg were zero after Week 4.

The World Health Organization (WHO) has approved, and BioMarin was issued, the International Nonproprietary Name (INN) “valoctocogene roxaparvovec” for the Company’s gene therapy to treat hemophilia A. INNs identify pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic name.

BioMarin has commissioned its gene therapy manufacturing facility, located in Novato, California. Good Manufacturing Practices (GMP) production of valoctocogene roxaparvovec has commenced and is intended to support clinical development activities and anticipated commercial demand, upon product approval. This facility is capable of supporting the manufacturing of product for approximately 2,000 patients per year, and the production process was developed in accordance with International Conference on Harmonisation guidance for Pharmaceuticals for Human Use facilitating worldwide registration with health authorities.

Pegvaliase for phenylketonuria (PKU): BioMarin announced that the pegvaliase Biologics License Application (BLA) remains on track for FDA action during the first half of 2018. The Company plans to submit a Marketing Authorization Application to the European Medicines Agency in the first quarter of 2018. Pegvaliase is a PEGylated recombinant phenylalanine ammonia lyase enzyme product that reduces blood phenylalanine (Phe) levels in adult patients with PKU who have uncontrolled blood Phe levels on existing management.

Vosoritide for achondroplasia: BioMarin provided an update on its open-label Phase 2 study of vosoritide, an analog of C-type Natriuretic Peptide (CNP), in children with achondroplasia, the most common form of disproportionate short stature in humans.

Vosoritide for achondroplasia has demonstrated sustained increase in average growth velocity over 30 months of treatment in 10 children, who completed 30 months of daily dosing at 15 µg/kg/day. Over this period of time, patients experienced mean absolute growth increase of approximately 4 cm over what their baseline growth velocity would have predicted.

The sustained increase in annualized growth velocity was accompanied by sustained improvements over time in height compared to age- and gender-matched unaffected children as measure by z-scores. In addition, treatment with vosoritide shows continued improvement over time in proportionality as measured by a ratio of the upper and lower body measurements, or U/L ratio.

The ongoing, global Phase 3 study is a randomized, placebo-controlled study of vosoritide in approximately 110 children with achondroplasia ages 5-14 for 52 weeks. The study will be followed by a subsequent open-label extension. Children in this study will have completed a minimum six-month baseline study to determine their respective baseline growth velocity prior to entering the Phase 3 study. Vosoritide is being tested in children in the age range where their growth plates are still open. This is approximately 25 percent of people with achondroplasia. The Company expects to complete enrollment of the Phase 3 study in mid-2018 and provide top-line data in the second half of 2019.

Given the importance of early intervention in this indication, at R&D Day, the Company announced that it will begin an infant/toddler study in the first half of 2018 in children ages 0-5 years old.

BMN 250 for MPS IIIB (Sanfilippo Syndrome, Type B): The Company discussed preliminary results from the Phase 1/2 trial with BMN 250 that demonstrated reduced heparan sulfate (HS) levels, a biomarker in the cerebrospinal fluid (CSF), in the brains of affected children. BMN 250, is an investigational enzyme replacement therapy using a novel fusion of recombinant human alpha-N-acetylglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2), for the treatment of Sanfilippo B syndrome or mucopolysaccharidosis IIIB (MPS IIIB). Discovered by BioMarin, BMN 250 is being studied in a multicenter, international clinical trial evaluating safety and tolerability, as well as cognitive function of patients with Sanfilippo B receiving BMN 250. Designed to restore functional NAGLU activity in the brain, BMN 250 is administered via intracerebroventricular (ICV) infusion.

In the completed dose escalation portion of the study (Part 1), which was primarily designed to determine safety and pharmacodynamic activity of BMN 250, three patients received escalating doses (30mg, 100mg, 300mg) of BMN 250 over 9 to12 months. CSF HS levels, which were markedly elevated at baseline, were reduced to the non-affected or normal range in all three patients, whether assessed as total or disease-specific HS. Sanfilippo B patients are missing one of four enzymes for HS degradation.

In those same patients, abdominal MRI scans showed significantly enlarged liver size at baseline followed by rapid decreases in liver size into the normal range for age with BMN 250 treatment, suggesting that ICV-administered BMN 250 reaches the peripheral circulation and may have activity in somatic organs. In contrast, most Sanfilippo B patients enrolled in BioMarin’s concurrently-running observational study (250-901) had increased liver size at baseline and experienced further increases in liver size over time. Two of the three treated patients from the dose escalation arm showed stabilization or some improvement compared to their pre-dose baselines in cognitive Development Quotient (DQ), a measure of cognitive function normalized to age. Patients with untreated Sanfilippo B usually show progressive decline in DQ.
Conference Call Details

BioMarin will host a conference call and webcast to discuss third quarter 2017 financial results today, Thursday, October 26, 2017 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

U.S. / Canada Dial-in Number: 866.502.9859
International Dial-in Number: 574.990.1362
Conference ID: 96054850

Replay Dial-in Number: 855.859.2056
Replay International Dial-in Number: 404.537.3406
Conference ID: 96054850

On October 26, 2017 Cytokinetics, Incorporated (Nasdaq:CYTK) reported total revenues for the third quarter of 2017 were $6.2 million, compared to $59.0 million, during the same period in 2016. Net loss for the third quarter was $32.4 million, or $0.60 per basic and diluted share, respectively, compared to net income for the same period in 2016 of $33.4 million, or $0.84 and $0.77 per basic and diluted share, respectively (Press release, Cytokinetics, OCT 26, 2017, View Source [SID1234521210]). As of September 30, 2017, cash, cash equivalents and investments totaled $308.2 million.

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“We are proud of the key milestones we recently achieved in preparation for the planned release of results from VITALITY-ALS, and potential regulatory filings and commercialization of tirasemtiv in North America and Europe,” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “In the third quarter, we also advanced CK-2127107 into two additional mid-stage clinical trials, one in patients with ALS and another in elderly subjects with limited mobility; we look forward to data from four clinical trials in this program in 2018. Finally, we are pleased that patient enrollment in GALACTIC-HF continues on target and commenced in Japan triggering a $10 million milestone payment to Cytokinetics.”

Recent Highlights and Upcoming Milestones

Skeletal Muscle Program

tirasemtiv (fast skeletal muscle troponin activator)

Completed dosing of patients in VITALITY-ALS (Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a Year in ALS), our Phase 3 clinical trial of tirasemtiv in patients with ALS.

Continued enrollment in VIGOR-ALS (Ventilatory Investigations in Global Open-Label Research in ALS), an open-label clinical trial designed to assess the long-term safety and tolerability of tirasemtiv in patients with ALS who have completed participation in VITALITY-ALS.

Conducted clinical, regulatory, non-clinical and other activities intended to support potential regulatory filings and registration of tirasemtiv in North America and Europe.

Conducted manufacturing, logistical planning, market research, market access and other commercial readiness activities intended to support potential registration and commercialization of tirasemtiv in North America and Europe.

Proceeding to collection of final data from VITALITY-ALS and clinical trial database lock in Q4 2017. We plan to conduct analyses of data from VITALITY-ALS and present results from this clinical trial on December 8, 2017 at the 28th International Symposium on ALS/MND in Boston.

Expect to continue to enroll patients who complete VITALITY-ALS into VIGOR-ALS throughout 2017.

CK-2127107 (next-generation fast skeletal muscle troponin activator)

Announced the start of a Phase 1b, double-blind, randomized, placebo-controlled, multiple dose, two-period crossover study to assess the effect of CK-2127107 on measures of physical function in elderly adults with limited mobility. This study is being conducted by Astellas, in collaboration with Cytokinetics.
Announced the start of FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS). This Phase 2 clinical trial is designed to assess the change from baseline in the percent predicted slow vital capacity (SVC) and other measures of skeletal muscle function after 12 weeks of treatment with CK-2127107 in patients with ALS. This trial is being conducted by Cytokinetics, in collaboration with Astellas.
“Reasons for Screen Failures and Baseline Characteristics of Randomized Patients from the First Cohort of the Phase 2 Clinical Trial of CK-2127107 in Patients with SMA,” presented by Stacy Rudnicki, M.D., Director, Clinical Research, Cytokinetics, at the Cure SMA 2017 Annual SMA Conference in Orlando, FL.
Expect to complete enrollment of Cohort 2 of the Phase 2 clinical trial of CK-2127107 in patients with SMA in 2017.
Expect data from the Phase 2 clinical trial of CK-2127107 in patients with SMA in Q1 2018.
Expect Astellas to continue enrollment in a Phase 2 clinical trial of CK-2127107 in patients with COPD in 2017.
Expect Astellas to continue enrollment in a Phase 1b clinical trial of CK-2127107 in adults with limited mobility in 2017.

Expect to continue enrollment in FORTITUDE-ALS, a Phase 2 clinical trial of CK-2127107 in patients with ALS in 2017.
Cardiac Muscle Program

omecamtiv mecarbil (cardiac muscle myosin activator)

Announced that the Phase 2 clinical trial of omecamtiv mecarbil in Japanese patients with heart failure met its pharmacokinetic primary endpoint and demonstrated statistically significant improvements in systolic ejection time (SET), a secondary endpoint.

Announced that the first patient has been dosed in Japan in GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil which is being conducted by Amgen, in collaboration with Cytokinetics. Coincident with patient dosing in Japan, Cytokinetics earned a $10 million milestone payment from Amgen.

Announced that additional results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase 2 trial evaluating omecamtiv mecarbil in patients with chronic heart failure, were presented by John Teerlink, M.D., Professor of Clinical Medicine at the University of California San Francisco and Director of Heart Failure at the San Francisco Veterans Affairs Medical Centers in a Rapid Fire Abstracts Presentation at the 21st Annual Heart Failure Society of America Scientific Meeting in Dallas, TX. The results suggest that omecamtiv mecarbil may produce similar results with regard to cardiac function, heart rate, biomarkers and adverse events in patients with ischemic and non-ischemic heart failure due to left ventricular systolic dysfunction.

Continued to enroll patients in GALACTIC-HF, the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil, conducted by Amgen, in collaboration with Cytokinetics.

Expect continued enrollment of patients with chronic heart failure in GALACTIC-HF throughout 2017.
Pre-Clinical Research

Continued research activities under our joint research program with Amgen directed to the discovery of next-generation cardiac muscle activators and under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators. In addition, company scientists continued independent research activities directed to our other muscle biology programs.
Expect to nominate at least 2 compounds from ongoing Research programs (partnered and unpartnered) as potential drug candidates by the end of 2017.
Financials

Revenues for the three and nine months ended September 30, 2017 were $6.2 million and $13.4 million, respectively, compared to $59.0 million and $73.3 million for the corresponding periods in 2016. Revenues for the first nine months of 2017 included the $10 million milestone payment from Amgen as well as $8.8 million of research and development revenues and $6.7 million of license revenues from our collaboration with Astellas and $1.3 million of research and development revenues from our collaboration with Amgen. Revenues for the first nine months of 2017 were offset by $13.8 million (out of the total of $40 million) for payments to Amgen related to our option to co-fund the Phase 3 development program of omecamtiv mecarbil in exchange for an increased royalty upon potential commercialization. Revenues in 2016 were primarily due to license revenue from the September 2016 expansion of our collaboration with Astellas. Astellas paid us $65 million in connection with the expanded collaboration.

Total research and development expenses for the three and nine months ended September 30, 2017 increased to $24.9 million and $64.0 million, respectively, from $17.9 million and $41.1 million for the same periods in 2016, primarily due to increased clinical activity, including activity for VITALITY-ALS and other activities intended to support potential regulatory filings and registration of tirasemtiv in North America and Europe, increased CK-2127107 clinical trials activity, as well as increased personnel.

General and administrative expenses for the three and nine months ended September 30, 2017 increased to $9.7 million and $26.2 million from $7.2 million and $21.1 million for the same periods in 2016, primarily due to increased personnel, non-cash stock compensation expense and commercial readiness activities.

Financial Guidance

The Company also announced updated financial guidance for 2017. The Company anticipates cash research and development expenses will be in the range of $103 to $107 million, cash revenue will be in the range of $16 to $18 million, and cash general and administrative expenses will remain in the range of $30 million to $32 million.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s third quarter results via a webcast and conference call today at 4:30 PM Eastern Time. The webcast can be accessed through the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 46689063.

An archived replay of the webcast will be available via Cytokinetics’ website until November 2, 2017. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 46689063 from October 26, 2017 at 7:30 PM Eastern Time until November 2, 2017.

On October 26, 2017 4SC AG (4SC, FSE Prime Standard: VSC) reported an interim communication on the nine months ended 30 September 2017 that presents all material developments with a focus on Q3 2017 and provides the Company’s current outlook (Press release, 4SC, OCT 26, 2017, View Source [SID1234521182]). The full communication is available for download on 4SC’s website.
Jason Loveridge, Ph.D., CEO of 4SC, commented:

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"With the conclusion of a successful capital increase generating gross proceeds of ca. EUR 41 million we are now well positioned to reach our stated goals over the next few years: to create significant value for our shareholders by executing on accelerated routes to market for our core cancer products resminostat, 4SC-202 and 4SC-208.

We will continue to enroll patients in our pivotal RESMAIN study of resminostat in cutaneous T-cell lymphoma (CTCL) and are looking forward to the initiation of a Phase II study of resminostat in patients with biliary tract cancer by our Japanese development partner Yakult Honsha Co., Ltd. (Yakult Honsha).

After opening the first clinical center within our SENSITIZE study of 4SC-202 in combination with a checkpoint inhibitor in melanoma patients in Q3 2017, we are anticipating to enroll the first patient in Q4 2017. Furthermore, we are expecting the investigator-initiated Phase II EMERGE study of 4SC-202 in combination with another checkpoint inhibitor in patients with microsatellite-stable gastrointestinal tumors to be initiated in Q1 2018.

Formal preclinical testing of 4SC-208 in order to initiate Phase I clinical evaluation is ongoing according to plan.

Finally, we aim to continue to enhance the value of 4SC and to add to our funds through signing deals with the right industry partners to pursue further development of our non-core assets as we did with the Kv1.3 inhibitors which we recently licensed to Maruho Co., Ltd. (Maruho)."

Key highlights of Q3 2017 and beyond

Ca. EUR 41 million secured from successful capital increase; proceeds forecast to be sufficient to finance 4SC’s accelerated development strategy into 2020
Patient enrollment and opening of study centers well on track for the ongoing pivotal RESMAIN study, which examines the potential of resminostat as maintenance therapy in patients with advanced CTCL
Preclinical data presented on resminostat’s potential to significantly alleviate itching in CTCL patients – one of the major disease burdens
Promising results of a Phase I study of resminostat in combination with S-1 chemotherapy in Japanese patients with biliary tract or pancreatic cancer presented by Yakult Honsha, 4SC’s development partner for resminostat in Japan
Phase Ib/II study SENSITIZE of 4SC-202 in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab (Keytruda(R), Merck) in patients with advanced-stage melanoma initiated with the opening of the first study centers
US composition of matter patent secured for structurally related compounds including 4SC-208; preclinical testing ongoing
Preclinical inhibitors of the Kv1.3 ion channel out-licensed to Maruho in return for up to EUR 208 million in upfront, development and commercial milestones plus single-digit royalties
Business outlook

Continue patient enrollment in the pivotal RESMAIN study of resminostat in CTCL
Yakult Honsha to initiate Phase II study of resminostat in Japanese patients with biliary tract cancer
Enroll patients in the Phase Ib/II study SENSITIZE of 4SC-202 in melanoma
Initiate Phase II investigator-initiated study EMERGE of 4SC-202 in patients with microsatellite-stable gastrointestinal tumors
Continue preclinical testing of 4SC-208 to initiate a Phase I clinical study immediately thereafter
Pursue further licensing deals for non-core assets and continue evaluating potential partnering opportunities with pharmaceutical and biotech companies to progress the clinical development of 4SC’s core pipeline assets
Development of cash balance in Q3 2017 and financial forecast

As of 30 September 2017, 4SC holds cash balance/funds of EUR 43,353 thousand as compared to EUR 4,638 thousand as of 30 June 2017. The increase results from a successful cash capital increase in July with gross proceeds of ca. EUR 41 million. The monthly use of cash from operations was within the range forecasted for 2017 amounting to EUR 739 thousand on average in the first nine months of 2017 (9M 2016 EUR 857 thousand). The decrease in 2017 was mainly driven by the upfront payment from the licensing agreement with Maruho offset by an increase in expenses for the preparation of the Phase Ib/II clinical study SENSITIZE of 4SC-202. The Management Board of 4SC confirms that the proceeds of the capital raise will finance 4SC’s stated goals into 2020.

Conference Call

4SC will not hold a telephone conference along with today’s Q3 2017 Interim Communication. According to 4SC’s policy, the Company will only hold conference calls when there is significant or material newsflow.

Further information

About resminostat

Resminostat is orally administered and potentially offers a novel approach to treating a wide variety of cancers, both as monotherapy and in combination therapy with other anti-cancer drugs. Resminostat inhibits tumor growth and proliferation, causes tumor regression, and strengthens the body’s immune response to cancer.

Resminostat has been shown to be well tolerated in several clinical trials. Resminostat is currently being investigated in a Phase II pivotal study in cutaneous T-cell lymphoma (CTCL) by 4SC. A Phase II study in biliary tract cancer is planned by 4SC’s development partner Yakult Honsha in Japan. Amongst others, resminostat has previously been investigated in biliary tract or pancreatic cancer and hepatocellular carcinoma (HCC).

About 4SC-202

4SC-202 is an orally administered small molecule with a unique mode of action that was designed to strengthen the body’s own anti-tumor immune response, open the tumor microenvironment and encourage infiltration of immune cells into the tumor.

4SC-202 has been investigated in a Phase I study with 24 mostly heavily pretreated patients with several types of highly advanced hematologic cancers, and was proven to be tolerated. Positive signs of anti-tumor efficacy were observed with one complete remission for 28 months and one partial responder for 8 months.

In addition to its therapeutic potential in cancer monotherapy, 4SC is evaluating 4SC-202’s capacity as a partner in combination therapies, specifically in the immuno-oncology area. In this respect, 4SC initiated a Phase Ib/II study of 4SC-202 in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab in patients with advanced-stage melanoma. A second Phase II study of 4SC-202 in combination with the anti-PD-L1 checkpoint inhibitor avelumab, which will be conducted by an academic partner in gastrointestinal cancers, is expected to start soon.

As soon as results from the aforementioned trials will be available, 4SC plans to advance 4SC-202 into a pivotal study in combination with a checkpoint inhibitor in PD-(L)1 refractory patients with advanced Merkel cell carcinoma (MCC).

About 4SC-208

Data from several preclinical in vivo models has established the efficacy of 4SC-208 in inhibiting the Hedgehog/GLI signaling. Inhibition of this signaling pathway has emerged as a highly effective strategy in obstructing the tumorigenic capacity of cancer stem cells, as well as tumor development, proliferation and survival.

Available inhibitors of Hedgehog signaling target the pathway upstream of the transcription factor GLI, whereas 4SC-208 inhibits at the level of GLI and is thus potentially able to avoid the tumor recurrence and relapse observed in response to currently available inhibitors.

4SC believes that 4SC-208 is a promising drug candidate and expects to complete formal preclinical testing in 2018 and to enter into a Phase I/II clinical study immediately thereafter. Cancer indications that are particularly promising are those where resistance to therapies targeting the Hedgehog/GLI pathway are emerging, such as in basal cell carcinoma.