On February 19, 2019 Alkermes plc (Nasdaq: ALKS) and Clovis Oncology, Inc. (Nasdaq: CLVS) reported that the companies have entered into a research collaboration to evaluate ALKS 4230, Alkermes’ investigational engineered interleukin-2 (IL-2) variant immunotherapy, in combination with rucaparib, Clovis’ marketed PARP inhibitor, and lucitanib, Clovis’ investigational tyrosine kinase inhibitor (Press release, Clovis Oncology, FEB 19, 2019, View Source [SID1234533389]). The collaboration will explore the potential anti-cancer effects of both treatment combinations in preclinical models across multiple tumor types. Results of this research may form the basis for potential future clinical studies of the novel combinations of ALKS 4230 with rucaparib and/or lucitanib.

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"Our preclinical partnership with Clovis reflects our ongoing efforts to explore the numerous combination options afforded to ALKS 4230. The collaboration will allow us to examine combinations in two areas of keen interest, PARP and tyrosine kinase inhibition pathways," said Mark Namchuk , Ph.D., Senior Vice President, Research, Pharmaceutical and Non-Clinical Development at Alkermes. "Evidence of combined benefit of ALKS 4230 with rucaparib and/or lucitanib from these preclinical studies may provide a strong rationale to advance into clinical development."

"The unique profiles of rucaparib, lucitanib and ALKS 4230 may offer the potential for complementary therapies that could represent a meaningful opportunity for the development of new anti-cancer combination treatment options," said Patrick J. Mahaffy , President and CEO of Clovis Oncology . "We are committed to exploring combinations such as these with Alkermes in order to bring improved therapeutic outcomes to patients with multiple tumor types."

Under this collaboration agreement, Alkermes and Clovis will perform preclinical studies to examine the mechanism of action and efficacy of the combinations of ALKS 4230 with rucaparib and ALKS 4230 with lucitanib in multiple tumor models. Under the terms of the agreement, the companies will share costs related to the preclinical studies, and each will contribute their respective compounds to the research collaboration.

About ALKS 4230
ALKS 4230 is an investigational, novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About Rucaparib
Rucaparib is an oral, small molecule inhibitor of the poly (ADP-ribose) polymerase (PARP) enzymes PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. Rucaparib stimulates an anti-tumor immune response through the activation of the stimulator of interferon ( STING ) pathway and tumor cell death, resulting in the infiltration of multiple immune subsets including CD8 positive T-cells. 1

Rucaparib is being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for rucaparib. Rucaparib is an unlicensed medical product outside of the U.S. and Europe .

About Lucitanib
Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3).

Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. 2 Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. 3 Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

On February 19, 2019 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported its financial results and corporate update for the quarter and full year ended December 31, 2018 (Press release, Ultragenyx Pharmaceutical, FEB 19, 2019, View Source [SID1234533390]).

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"This last year was important for Ultragenyx as we successfully launched two therapies internationally and validated clinical data from our gene therapy platform," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "In 2019 we look forward to expanding the global commercial reach of our approved therapies, submitting a New Drug Application for a third, and advancing our gene therapy platform toward pivotal studies."

Fourth Quarter and Full Year 2018 Financial Results

Net Revenues

For the fourth quarter of 2018, Ultragenyx reported $16.3 million in total revenue. Ultragenyx recognized $11.6 million in total Crysvita revenue. This includes $9.9 million in collaboration revenue in the U.S. profit share territory and $1.3 million in royalty revenue in the European territory from the collaboration and license agreement with Kyowa Hakko Kirin. Net product sales for Crysvita in other regions were $0.4 million. Mepsevii (vestronidase alfa) product revenue for the fourth quarter of 2018 was $2.7 million, and UX007 named patient revenue was $0.5 million. Ultragenyx recognized $1.6 million in revenue from its research agreement with Bayer.

Net revenue for the year ended December 31, 2018 totaled $51.5 million. Since launching Crysvita on April 27, 2018 through the end of the year, Ultragenyx recognized $18.9 million in total Crysvita revenue. This includes $15.3 million in collaboration revenue in the U.S. profit share territory and $2.9 million in royalty revenue in the European territory from the collaboration and license agreement with Kyowa Hakko Kirin. Net product sales for Crysvita in other regions totaled $0.6 million. Mepsevii product revenue for the year ended December

31, 2018 was $7.9 million and UX007 named patient revenue was $1.3 million. Ultragenyx recognized $23.5 million in revenue from its research agreement with Bayer in the year ended December 31, 2018.

Operating Expenses

Total operating expenses for the fourth quarter of 2018 were $106.6 million compared with $99.2 million for the same period in 2017, including non-cash stock-based compensation of $21.1 million and $19.5 million in the fourth quarter of 2018 and 2017, respectively. Total operating expenses for the year ended December 31, 2018, were $422.9 million compared with $331.6 million for the same period in 2017, including non-cash stock-based compensation of $80.1 million and $68.0 million in the full year of 2018 and 2017, respectively. The increase in total operating expenses is due to the increase in commercial, development, and general and administrative costs as the company commercializes, grows and advances its pipeline.

For the fourth quarter of 2018, Ultragenyx reported a net loss of $87.8 million, or $1.73 per share, basic and diluted, compared with a net loss for the fourth quarter of 2017 of $81.7 million, or $1.89 per share, basic and diluted. For the year ended December 31, 2018, net loss was $197.6 million, or $3.97 per share, basic and diluted, compared with a net loss for the same period in 2017 of $302.1 million, or $7.12 per share, basic and diluted. The loss from the full year 2018 was reduced by the sale of the Mepsevii (vestronidase alfa) priority review voucher (PRV) in January 2018 for net proceeds of $130.0 million and a $40.3 million gain from Ultragenyx’s portion of the sales of the PRV received with the Crysvita (burosumab) approval. The net loss for the full year 2018 reflected cash used in operations of $290.6 million compared to $253.8 million for the same period in 2017.

Cash, Cash Equivalents and Investments

Cash, cash equivalents and investments were $459.7 million as of December 31, 2018.

Recent Updates

Crysvita in X-Linked Hypophosphatemia (XLH)

Longer-term data from the Phase 3 pediatric study demonstrated superior efficacy of Crysvita compared with conventional oral phosphate treatment. After 64 weeks of treatment, patients treated with Crysvita continued to show significantly greater improvement in healing of rickets, growth, and bowing of the legs compared with patients treated with oral phosphate and active Vitamin D, which was the standard of care for over 30 years. The 64-week safety profile was similar to that observed at 40 weeks and in other Crysvita pediatric XLH studies.

Crysvita was approved and launched in Canada for the treatment of XLH in adults and pediatric patients one year of age and older. Canada is included in the North American profit share agreement with our partner Kyowa Hakka Kirin.

UX007 in Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

Positive topline data from ongoing long-term extension study of UX007 for the treatment of LC-FAOD showed sustained reductions in the duration and frequency of major clinical events (MCEs), primarily hospitalizations for hypoglycemia, cardiomyopathy, and rhabdomyolysis. Patients who had previously been enrolled in the Company-sponsored Phase 2 study (n=24) demonstrated sustained reductions in MCEs after an additional 78 weeks of treatment, and 20 additional patients who had not previously received UX007 demonstrated similar substantial reductions in these MCEs with treatment, further corroborating prior results. The safety profile was consistent with what has been previously observed with UX007.

DTX401 Gene Therapy in Glycogen Storage Disease Type Ia (GSDIa)

Positive topline results from the first cohort of the Phase 1/2 clinical study of DTX401 gene therapy in GSDIa. All three patients demonstrated a clinical response, reflected by improved glucose control, increased time to hypoglycemia during fasting and reductions in necessary cornstarch dosing. Two patients demonstrated a clinically meaningful improvement in time to hypoglycemia, making it possible to sleep through the night. Typically, for GSDIa patients, cornstarch or tube feeding is required during the night to prevent severe hypoglycemia, which can cause seizures or death. There were no infusion-related adverse events and no treatment-related serious adverse events reported.

Upcoming Key Milestones

UX007 in LC-FAOD

Ultragenyx is on track to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in mid-2019. The submission will include data from the company-sponsored Phase 2 study in 29 patients, data from the long-term efficacy and safety extension study in 75 patients, a retrospective medical record review of 20 original compassionate use patients, data from 70 patients treated through expanded access, and a randomized controlled investigator-sponsored study of 32 patients showing an effect of UX007 on cardiac function.

DTX301 Gene Therapy in Ornithine Transcarbamylase (OTC) Deficiency

Enrollment is ongoing in the third-dose cohort of the Phase 1/2 study. Cohort 3 data expected in mid-2019.

DTX401 Gene Therapy in GSDIa

Enrollment is ongoing in the second-dose cohort of the Phase 1/2 study. Cohort 2 data expected in mid-2019.

Corporate

Ultragenyx plans to host an Analyst Day on Wednesday, April 17. The event will provide updates and expert commentary on commercial, clinical stage and early pipeline programs. Additional details to come.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Tuesday, February 19, 2018, at 2 p.m. PT/ 5 p.m. ET to discuss fourth quarter and full year 2018 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 6689186. The replay of the call will be available for one year.

On February 19, 2019 Zetagen Therapeutics, Inc., a private, US-based biopharmaceutical company dedicated to driving breakthrough innovation in the treatment of metastatic bone cancers and orthopedic interventions, reported that the U.S. Patent and Trademark Office ("USPTO") has issued U.S. Patent No. 10208306 and the South African Patent Office issued PCT. 2017/00029 to the Company (Press release, Zetagen Therapeutics, FEB 19, 2019, View Source [SID1234643687]). These patents, entitled Composition and Methods to Promote Bone Formation, include claims covering the use of methods for stimulating bone growth using its novel molecular pathway, ZetaMet (Zeta-BC-003). ZetaMet (Zeta-BC-003) is a synthetic, small molecule, inductive biologic, delivered via a drug-eluting implant on an osteopromotive carrier.

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"These new patent issuances are an important step forward towards our ultimate goal of obtaining the global, commercial rights for our treatments," said Joe C. Loy, CEO of Zetagen Therapeutics, Inc. "We believe in the potential our therapies hold for patients around the world who live with debilitating metastatic bone cancers."

The new patent is part of an expanding and comprehensive portfolio of patents, patent applications and other intellectual property covering the composition, synthesis, manufacturing, formulations and uses for the treatment of a variety of metastatic bone lesions and osteologic interventions. Zetagen exclusively licensed its platform technology from the State University of New York in 2016.

On February 19, 2019 National Brain Tumor Society (NBTS), a leading nonprofit dedicated to the brain tumor community in the United States, reported a new partnership with the Brain Science Foundation (BSF) (Press release, National Brain Tumor Society, FEB 19, 2019, View Source [SID1234553933]). Under terms of the partnership, the organizations have established the Meningioma Research Fund to raise and grant funds specifically for meningioma research poised to identify and advance treatments aimed at dramatically improving survival and quality of life.

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Meningioma is the most common primary brain tumor, accounting for 37 percent of all brain tumor diagnoses and approximately 30,000 new cases every year in the United States. There are fifteen types of meningiomas presenting a wide range of physical, emotional, and occupational challenges – and can ultimately be life-threatening.

"Given the legacy of the Brain Science Foundation and its association with meningioma, and our shared goals with the National Brain Tumor Society to fund research aimed to advance the development of treatments, it quickly became evident that the community of patients, advocates, and healthcare providers could benefit from a formal collaboration between our respective organizations," says Steven Haley, founder of the Brain Science Foundation. "We believe NBTS’s depth and breadth of assistance, combined with the continuity of the BSF mission on a larger platform will be compelling and welcomed in the community we serve."

The Meningioma Research Fund creates an opportunity for donors specifically interested in supporting research on this tumor type to join together to scale up the impact of their philanthropy.

"Medical research directed toward meningioma is disproportionately small compared to other brain tumor types," says David Arons, Chief Executive Officer, National Brain Tumor Society. "Yet, meningiomas can be life-altering and cause lasting deficits to patients, as the only treatment option for many is invasive brain surgery. This partnership with the Brain Science Foundation and the creation of the Meningioma Research Fund will allow us to invest in best-in-class science and accelerate research that is aimed at advancing better treatment options for these patients."

The Brain Science Foundation was established in 2002 and has gone on to fund nearly $1 million annually in support of outstanding physician-scientists in brain tumor research, with a particular focus on meningioma. To date, BSF-funded researchers have impacted lives through a variety of research programs that have included the creation of advanced diagnostic tools, surgical instruments and techniques, post-operative care protocols and therapies that are less invasive but more effective.

About Meningioma

Meningioma is the most common primary brain tumor, accounting for 37.1 percent of all brain tumor diagnoses. It is estimated that 31,990 individuals will be diagnosed with a meningioma in the United States in 2019. Meningioma is most commonly diagnosed in adults, with an average age at diagnosis of 66, and is more common in women than men. African Americans are significantly more likely than Caucasians to develop meningioma. The 10-year relative survival rate for all meningioma patients is 81.5 percent, but only 53.5 percent for those with a malignant meningioma.

On February 19, 2019 Acorda Therapeutics, Inc. (Nasdaq:ACOR) reported that Andrew Hindman, Acorda’s Chief Business Officer, will present at the Leerink Global Healthcare Conference on Wednesday, February 27 at 11:00 a.m. EST (Press release, Acorda Therapeutics, FEB 19, 2019, View Source [SID1234533465]). A live audio webcast of the presentation can be accessed under "Investor Events" in the Investor section of the Acorda website at www.acorda.com, or you may use the link:

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