Exact Sciences to participate in March investor conferences

On February 26, 2020 Exact Sciences Corp. (Nasdaq: EXAS) reported that company management will participate in the following investor conferences and invited investors to participate by webcast (Press release, Exact Sciences, FEB 26, 2020, View Source [SID1234554805]).

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Cowen 40th Annual Health Care Conference, Boston
Fireside Chat on Monday, March 2, 2020, at 1:30 p.m. EST

Barclays Global Healthcare Conference, Miami
Fireside Chat on Tuesday, March 10, 2020, at 3:50 p.m. EDT
The webcast can be accessed in the investor relations section of Exact Sciences’ website at www.exactsciences.com.

Portola Pharmaceuticals Reports Fourth Quarter and Full-Year 2019 Financial Results
and Provides Corporate Update

On February 26, 2020 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported financial results for the fourth quarter and full year ended December 31, 2019 (Press release, Portola Pharmaceuticals, FEB 26, 2020, View Source [SID1234554804]).

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"2019 was a year of significant accomplishments for Portola with the launch of our Gen 2 formulation of Andexxa in the United States and the approval and launch of Ondexxya in Europe. In 2020 we have several catalysts that we expect to drive further adoption and growth worldwide," said Scott Garland, Portola’s president and chief executive officer. "This includes the presentation of new clinical data, enhanced education and support related to reimbursement, the initiation of our urgent surgery study, and continued execution of the Ondexxya launch in Europe. Combined with the robust growth in the Factor Xa inhibitor market and our other strategic initiatives, we are confident that Andexxa has significant long-term growth potential."
Quarter Ending December 31, 2019, and Full-Year 2019 Financial Results

Total global revenues for the fourth quarter of 2019 were $29.2 million compared with $15.3 million for the fourth quarter of 2018. This includes $28.4 million in net product revenues from sales of Andexxa/Ondexxya [coagulation factor Xa (recombinant), inactivated-zhzo], and $0.9 million in collaboration and license revenues. Total global revenues for the full year 2019 were $116.6 million compared with $40.1 million for the full year 2018. This includes $111.5 million in net product revenues from sales of Andexxa/Ondexxya, and $5.0 million in collaboration and license revenues.

Net loss attributable to Portola was $96.7 million, or $1.24 net loss per share for the fourth quarter of 2019, compared with a net loss of $88.5 million, or $1.34 net loss per share, for the same period in 2018. Net loss attributable to Portola was $290.7 million, or $4.06 net loss per share for the full year 2019, compared with a net loss of $350.2 million, or $5.31 net loss per share, for the full year 2018. This includes the effect of a $27.5 million charge taken in the fourth quarter of 2019 for Bevyxxa inventory and manufacturing related to the decision to discontinue the commercialization of Bevyxxa, and a $3.2 million impairment charge taken in the second quarter of 2019 related to the discontinuation of our SRX program.

Non-GAAP net loss for the fourth quarter of 2019 was $58.3 million, or a non-GAAP basic and diluted loss per share of $0.75. For the full year 2019, non-GAAP net loss was $198.2 million, or a non-GAAP basic and diluted loss per share of $2.77. Non-GAAP net loss and loss per share have been adjusted to exclude the Bevyxxa inventory and manufacturing charge and an impairment charge as well as stock-based compensation expenses. Please see the reconciliation of GAAP to non-GAAP financial measures at the end of this release for more details.

Total operating expenses for the fourth quarter of 2019 were $119.4 million compared with $102.5 million for the same period in 2018. Total operating expenses for the full year 2019 were $387.9 million, compared with $385.5 million for the full year 2018.

Non-GAAP total operating expenses, which excludes the Bevyxxa inventory and manufacturing charge and impairment charge as well as stock based compensation expenses, were $81.1 million for the fourth quarter of 2019, and $295.5 million for the full year 2019. Please see the reconciliation of GAAP to non-GAAP financial measures table at the end of this release for more details.

Research and development (R&D) expenses were $29.9 million for the fourth quarter of 2019 compared with $49.5 million for the fourth quarter of 2018. R&D expenses for the full year 2019 were $124.6 million, compared with $216.2 million for the full year 2018. The decrease in both periods is primarily due to the manufacturing costs for Andexxa Gen 2 being capitalized and no longer flowing through R&D.

Selling, general and administrative (SG&A) expenses for the fourth quarter 2019 were $60.0 million compared with $40.6 million for the fourth quarter of 2018. SG&A expenses for the full year 2019 were $218.9 million compared with $151.2 million for the full year 2018. The increase in both periods is due to commercial costs to support the launch of Andexxa, including the expansion of the field sales teams and support for the launch of Ondexxya in Europe.

Cost of sales (COS) for the fourth quarter of 2019 was $29.6 million compared to $12.4 million for the same period in 2018. COS for the full year 2019 was $44.4 million compared with $18.1 million for the full year 2018. The increase in both periods is due to a charge for Bevyxxa inventory and manufacturing as the Company winds down that program.

Please see the GAAP to non-GAAP reconciliation table at the end of this release for a detailed breakdown.
Cash, Cash Equivalents and Investments:

Cash, cash equivalents and investments at December 31, 2019, totaled $466.2 million, compared with $317.0 million as of December 31, 2018. During the fourth quarter, the Company drew down the remaining $62.5 million available under its $125.0 million loan agreement with HealthCare Royalty Partners (HCR) and investment funds manager Athyrium Capital Management, LP.
2020 Annual Financial Guidance
For the fiscal year 2020, Portola expects total R&D expenses to be between $105 million and $120 million, including stock-based compensation expenses of approximately $14 million. Portola expects total SG&A expenses to be between $235 million and $250 million, including stock-based compensation expenses of approximately $38 million.
Recent Achievements and Events

Completed an internal restructuring to align resources to drive Andexxa growth including the discontinuation of commercialization and partnering efforts for Bevyxxa. In addition, the Company has decided not to initiate the CELTIC-1 trial for the SYK/JAK inhibitor cerdulatinib until a partner is identified.

Initiated the single-arm urgent surgery study for Andexxa, ANNEXA-S.

Andexxa was highlighted as a first-line Factor Xa reversal option by the American College of Emergency Physicians in recommendations published in the Annals of Emergency Medicine, bringing the total number of guideline inclusions to 19.

Presented multiple abstracts related to cerdulatinib at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting in December. The data demonstrated good tolerability and clinical response in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), including a 52% overall response rate in patients with angioimmunoblastic T-cell lymphoma (AITL), and a 76% overall response rate in patients with follicular lymphoma treated with cerdulatinib in combination with rituximab.

Appointed 20-year industry veteran Rajiv Patni, M.D., as executive vice president and chief medical officer, with responsibility for leading Clinical Development, Clinical Operations, Medical Affairs, Regulatory Affairs, Biometrics, Pharmacovigilance and Project Management.

Launched a partnership with the American Heart Association supporting its hospital-focused quality improvement initiative for enhanced awareness and understanding of best care practices for hemorrhagic stroke.
Planned Upcoming Milestones

Present and publish clinical, research and HEOR studies supporting the adoption of Andexxa at medical meetings and in peer-reviewed journals throughout the year, starting with the presentation of three abstracts at the American College of Cardiology 2020 Annual Meeting in March.

Secure reimbursement coverage in the United Kingdom (early 2H 2020), Germany (2H 2020) and other Wave 1 European countries.

Continue launch of Ondexxya into Wave 2 countries in Europe, which include the additional EU5 countries of France, Spain, and Italy.

Conference Call Details
Portola will host a conference call today, Wednesday, February 26, 2020, at 4:30 p.m. ET, during which time management will discuss the fourth quarter and full-year 2019 financial results, updates on the U.S. and European launches of Andexxa/Ondexxya, and its operations. The live call can be accessed by phone by calling (844) 452-6828 from the United States and Canada or 1 (765) 507-2588 internationally and using the passcode 6192918. The webcast can be accessed live on the Investor Relations section of the Company’s website at View Source It will be archived for 30 days following the call.

CYCLACEL PHARMACEUTICALS REPORTS FOURTH QUARTER AND FULL YEAR 2019 FINANCIAL RESULTS

On February 26, 2020 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported its financial results and business highlights for the fourth quarter and full year ended December 31, 2019 (Press release, Cyclacel, FEB 26, 2020, View Source [SID1234554803]). The Company’s net loss applicable to common shareholders for the three months and year ended December 31, 2019 was $2.4 million and $8.0 million, respectively. As of December 31, 2019, cash and cash equivalents totaled $11.9 million. Based on current spending, cash on hand provides the Company with sufficient resources to fund all planned operations including research and development through Q1 2021.

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"Our fadraciclib (CYC065) CDK inhibitor is establishing a leadership position among MCL1 suppressing compounds in clinical development," said Spiro Rombotis, President and Chief Executive Officer. "After enrolling approximately 60 patients to date with multiple dosing schedules in three Phase 1 dose escalation studies in patients with relapsed or refractory (R/R) solid tumors and hematological malignancies, we have demonstrated safety, proof of mechanism by durable suppression of MCL1 and anticancer activity of fadraciclib as single agent and in combinations. Encouragingly, a heavily pretreated patient with MCL1 amplified endometrial cancer has received over 10 cycles of fadraciclib monotherapy achieved a confirmed partial response (PR) and a further reduction in her target tumor lesions of 73%. Based on data thus far, we are developing a precision medicine strategy to further evaluate fadraciclib as monotherapy and in combinations. In our Phase 1 trial of a combination of fadraciclib and venetoclax in patients with relapsed or refractory AML/MDS, we have enrolled 11 patients and reached dose level five and in CLL 3 patients and dose level two. Our clinical stage pipeline, comprising of fadraciclib, sapacitabine and CYC140, our PLK1 inhibitor, is a central element of our strategy of building an innovative pipeline addressing cancer resistance and DNA damage response."

Key Corporate Highlights

·CYC065-01 Phase 1 part 2 single agent i.v. – In November 2019, we reported anticancer activity in a heavily pretreated a patient with MCL1 amplified endometrial cancer who achieved a radiographically confirmed partial response (PR) after 4 cycles at 213mg. The patient remains on study after 10 cycles and shrinkage of her target tumor lesions has reached 73%. An additional patient with cyclin E amplified ovarian cancer achieved stable disease after 4 cycles at 213mg with 29% tumor shrinkage. We are expanding the 213mg dose level to recruit additional patients and determine the recommended Phase 2 dose.

·CYC065-01 Phase 1 part 3 single agent p.o. – We are evaluating an oral capsule form of fadraciclib in patients with advanced solid tumors and have enrolled two patients at 75mg and 150mg once daily. Pharmacokinetic (PK) data in the two patients demonstrated a predictable PK profile closely overlapping the i.v. form with encouraging exposure levels.

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www.cyclacel.com – [email protected]

·CYC065-03 Phase 1 fadraciclib i.v. and venetoclax p.o. – We have dosed 11 heavily pretreated patients with R/R AML in five dose levels up to 200 mg/m2 in combination with the BCL2 inhibitor venetoclax. Evidence of anticancer activity has been observed in multiple patients with blast reductions in peripheral blood. Preclinical AML data demonstrated synergy of fadraciclib and venetoclax, suggesting that targeting both BCL2 and MCL1 may be more beneficial than inhibiting either protein alone.

·CYC065-02 Phase 1 fadraciclib i.v. and venetoclax p.o. – We have dosed 3 patients with R/R CLL in two dose levels up to 85 mg/m2 in combination with venetoclax. Evidence of anticancer activity has been observed in two patients who experienced reduction in lymph node size with one of them achieving MRD negative status. Preclinical CLL data demonstrated synergy of fadraciclib and venetoclax, suggesting that targeting both BCL2 and MCL1 may be more beneficial than inhibiting either protein alone.

·CYC682-11 Phase 1b/2 part 2 sapacitabine p.o. and venetoclax p.o.– We have enrolled 10 patients in two dose cohorts in our DNA Damage Response (DDR) program evaluating an oral combination of sapacitabine and venetoclax in patients with R/R AML/MDS. Sapacitabine is a nucleoside analogue that is active in AML and MDS R/R to prior therapy such as cytarabine or hypomethylating agents. Preclinical data demonstrated synergy of sapacitabine with BCL2 inhibition which may offer an effective, oral treatment regimen for patients who have failed front-line therapy.

·CYC140-01 Phase 1 CYC140 i.v. – We have enrolled 4 patients in our first-in-human, dose escalation study evaluating CYC140 in patients with advanced leukemias. CYC140 is a small molecule, selective polo-like-kinase 1 (PLK1) inhibitor that has demonstrated potent and selective target inhibition and high activity in xenograft models of human cancers.

More information on our clinical trials can be found at www.clinicaltrials.gov.

Key Business Objectives for 2020

·Report updated Phase 1 safety, PK and efficacy data for fadraciclib utilizing a frequent i.v. dosing schedule in patients with advanced solid cancers;

·Report initial safety and PK data from the Phase 1 study of an oral formulation of fadraciclib;

·Report initial safety and proof of concept data from the fadraciclib-venetoclax Phase 1 studies in R/R AML/MDS and CLL;

·Report initial data from the sapacitabine-venetoclax Phase 1b/2 study in patients with R/R AML/MDS;

·Report initial data from the CYC140 Phase 1 first-in-human study in R/R leukemias; and

·Report data from the Phase 1b/2 IST of sapacitabine-olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators.

Financial Highlights

As of December 31, 2019, cash and cash equivalents totaled $11.9 million, compared to $17.5 million as of December 31, 2018. The decrease of $5.6 million was primarily due to net cash used in operating activities of $9.4 million, offset by $3.8 million of net cash provided by financing activities.

Revenues for the three months and year ended December 31, 2019 amounted to $0 compared to $0.2 million for the same periods in 2018. The 2018 revenue related to a collaboration, licensing and supply agreement with ManRos Therapeutics, entered into in June 2015.

Research and development expenses were $1.4 million and $4.7 million for the three months and year ended December 31, 2019 as compared to $1.1 million and $4.3 million for the same periods in 2018. Research and development expenses relating to the transcriptional regulation, CDK inhibitor program with fadraciclib increased by $0.5 million from $2.5 million for the year ended December 31, 2018 to $3.0 million for the year ended December 31, 2019, as the clinical evaluation of fadraciclib progressed. Research and development expenses relating to the DDR, sapacitabine program decreased by $0.4 million from $0.9 million for the year ended December 31, 2018 to $0.5 million for the year ended December 31, 2019, primarily as a result of expenditure related to clinical trial drug supply manufacturing in 2018.

General and administrative expenses for the three months and year ended December 31, 2019 were $1.4 million and $5.0 million respectively, compared to $1.5 million and $5.4 million for the same periods of the previous year.

Total other income, net for the three months and year ended December 31, 2019 were $0.1 million and $0.6 million, compared to $0.1 million and $0.9 million for the same periods of the previous year. The decrease of $0.3 million for the year ended December 31, 2019 is primarily related to a reduction in income received under an Asset Purchase Agreement with ThermoFisher Scientific.

United Kingdom research & development tax credits were $0.4 million and $1.3 million for the three months and year ended December 31, 2019 as compared to $0.4 million and $1.3 million for the same periods in 2018.

Net loss for the three months and year ended December 31, 2019 were $2.3 million and $7.8 million compared to $2.0 million and $7.3 million for the same periods in 2018.

The Company raised net proceeds of approximately $4.1 million during 2019, from its Common Stock Sales Agreement with H.C. Wainwright, which is now completed.

The Company estimates that cash resources of $11.9 million as of December 31, 2019 will fund currently planned programs through the first quarter of 2021.

Conference call information:

US/Canada call: (877) 493-9121 / international call: (973) 582-2750

US/Canada archive: (800) 585-8367 / international archive: (404) 537-3406

Code for live and archived conference call is 6761906.

For the live and archived webcast, please visit the Corporate Presentations page on the Cyclacel website at www.cyclacel.com. The webcast will be archived for 90 days and the audio replay for 7 days.

Adaptive Biotechnologies Reports Fourth Quarter and Full Year 2019 Financial Results

On February 26, 2020 Adaptive Biotechnologies Corporation ("Adaptive Biotechnologies") (Nasdaq: ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, reported financial results for the fourth quarter and full year ended December 31, 2019 (Press release, Adaptive Biotechnologies, FEB 26, 2020, View Source [SID1234554802]).

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"During 2019, we drove strong topline growth in our commercial products and made critical progress advancing our clinical product pipeline," said Chad Robins, chief executive officer and co-founder of Adaptive Biotechnologies. "Looking ahead to 2020, we will continue to build our commercial infrastructure while also expanding the R&D resources required for immunoSEQ Dx and our Genentech alliance. We are confident that the scale with which we are able to map immune receptors to clinically relevant antigens will continue to advance the field of immune-driven medicine."

Recent Highlights

Revenue of $24.2 million for the fourth quarter and $85.1 million for the full year of 2019, representing 41% and 53% increases, respectively, over the corresponding periods in 2018

Clinical tests for clonoSEQ increased 66% to 3,218 clinical tests in the fourth quarter of 2019, compared to the fourth quarter 2018

Initiated two additional pharma partnerships with AbbVie and Genentech to measure MRD using the clonoSEQ assay as a clinical trial endpoint to potentially accelerate the development of venetoclax

Delivered a data package to Genentech for the company’s first selected T-cell receptor candidate that targets a shared cancer antigen expressed in multiple solid tumors

Fourth Quarter 2019 Financial Results

Revenue was $24.2 million for the quarter ended December 31, 2019, representing a 41% increase from the fourth quarter in the prior year. Sequencing revenue was $13.9 million for the quarter, representing a 33% increase from the fourth quarter in the prior year. Development revenue increased to $10.3 million for the quarter, representing a 53% increase from the fourth quarter in the prior year.

Operating expenses were $48.4 million for the fourth quarter of 2019, compared to $31.3 million in the fourth quarter of the prior year, representing an increase of 54%.

Net loss was $20.6 million for the fourth quarter of 2019, compared to $13.3 million for the same period in 2018.

Adjusted EBITDA (non-GAAP) was a loss of $18.7 million for the fourth quarter of 2019, compared to a loss of $9.5 million for the fourth quarter of the prior year.

Full Year 2019 Financial Results

Revenue was $85.1 million for the year ended December 31, 2019, representing a 53% increase from the prior year. Sequencing revenue was $43.5 million in 2019, representing a 32% increase from 2018. Development revenue increased to $41.6 million in 2019, representing an 83% increase from the prior year.

Operating expenses for 2019 were $163.5 million, compared to $105.4 million for 2018, representing an increase of 55%.

Net loss was $68.6 million in 2019, compared to $46.4 million in 2018.

Adjusted EBITDA (non-GAAP) was a loss of $57.5 million for 2019, compared to a loss of $32.6 million in the prior year.

Cash, cash equivalents and marketable securities was $682.3 million as of December 31, 2019.

2020 Financial Guidance

Management will provide the 2020 revenue outlook on the conference call scheduled to discuss the 2019 financial results.

Webcast and Conference Call Information

Adaptive Biotechnologies will host a conference call to discuss its fourth quarter and full year 2019 financial results after market close on Wednesday, February 26, 2020 at 4:30 PM Eastern Time. The conference call can be accessed live over the phone (800) 361-2311 for U.S. callers or (409) 937-8761 for international callers (Conference ID: 8845168). The webcast can be accessed at View Source

BioMarin Announces Fourth Quarter and Record Full-year 2019 Financial Results

On February 26, 2020 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the fourth quarter and full year 2019 (Press release, BioMarin, FEB 26, 2020, View Source [SID1234554801]).

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Total Net Product Revenues for the fourth quarter of 2019 increased to $436.6 million, compared to $347.2 million for the fourth quarter of 2018. The increase in Net Product Revenues was attributed to the following:
•Palynziq Net Product Revenues increased by $23.6 million, driven by a combination of revenue from patients achieving maintenance dosing and new patients initiating therapy. In the U.S. Palynziq received approval from the U.S. Food and Drug Administration (FDA) in May 2018 and launched in the third quarter of that year. Palynziq received approval in May 2019 from the European Commission (EC) and commercial sales in Europe commenced in the fourth quarter of 2019;
•Vimizim Net Product Revenues increased by $18.3 million, or 16%, driven primarily by patient growth in the U.S. and orders from Brazil;
•Naglazyme Net Product Revenues increased by $18.1 million, or 24%, primarily due to orders from Brazil;
•Brineura Net Product Revenues increased by $13.0 million, or 107%, due in large part by patient growth across all regions particularly Europe;
•Kuvan Net Product Revenues increased by $10.4 million, or 9%, primarily driven by an increase in patients in North America; and
•Aldurazyme Net Product Revenues increased $6.5 million, or 37%, due to higher sales volume to Sanofi Genzyme.
The increase in GAAP Net Income for the fourth quarter of 2019, compared to GAAP Net Loss for the same period in 2018 was primarily due to the following:
•increased gross profits of $80.3 million primarily driven by increased product sales; partially offset by
•higher selling, general and administrative (SG&A) expense related to pre-commercialization activities for valoctocogene roxaparvovec, and support of the EU commercial launch and continued U.S. expansion of Palynziq.
Non-GAAP Income for the fourth quarter of 2019 increased to $46.4 million, compared to Non-GAAP Loss of $10.9 million for the same period in 2018. The increase in Non-GAAP Income for the quarter, compared to the same period in 2018, was attributed to higher gross profit and decreased research and development expense, partially offset by higher SG&A expense.

As of December 31, 2019, BioMarin had cash, cash equivalents and investments totaling approximately $1.2 billion, as compared to $1.3 billion on December 31, 2018.
Commenting on 2019 results, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, said, "Our performance in 2019 reflects the clinical, regulatory and financial goals we set for ourselves a year ago. We completed enrollment of the Phase 3 Interim Analysis cohort with valoctocogene roxaparvovec and met the criteria for expedited review of marketing applications in the United States and Europe. With those applications now under review by global health authorities, we await the potential approval of valoctocogene roxaparvovec, the first gene therapy product to be reviewed for the treatment of severe hemophilia A. Another significant success in 2019 was the completion of and results from our global Phase 3 study with vosoritide for achondroplasia. With a high degree of statistical significance (p<0.0001) the primary endpoint of increase in growth velocity from baseline over a one year period was demonstrated with vosoritide. Based on these results, the Company plans to meet with health authorities in the first half of 2020 to discuss plans for submitting marketing applications later this year. Another study with

vosoritide, the global Phase 2 in infants and young children (less than 60 months old), is continuing enrollment. All subjects from ages 6 months through 5 years are almost completely enrolled. The youngest cohort, infants up to 6 months old, is actively enrolling. Interest in this study with very young children has been extremely robust, demonstrating that families are keen to seek treatment for their children as early as possible."
Mr. Bienaimé continued, "In addition to these later-stage regulatory and clinical milestones in 2019, we made significant progress advancing our early-stage pipeline. Building on the success of our phenylketonuria (PKU) franchise with Palynziq and Kuvan, we announced in January that both the United States and the United Kingdom health authorities had given the go-ahead to start dosing patients with PKU with our BMN 307 gene therapy in a Phase 1/2 study. We plan to treat patients with BMN 307 in the first quarter using product made at commercial scale from our award-winning gene therapy manufacturing facility. Other additions to the pipeline announced at R&D Day last November included, BMN 331 gene therapy for hereditary angioedema and vosoritide for dominantly inherited short stature. Finally, our most recently approved product, Palynziq for the treatment of PKU, continues along a very strong growth trajectory since approval in 2018 in the U.S. We have been very pleased with the pace of the U.S. launch, as we ended 2019 with 762 patients on reimbursed Palynziq, and an additional 143 naïve patients having completed enrollment and awaiting their first injection. Based on the tremendous interest in treatment with Palynziq, we provided full-year guidance for Palynziq Net Product Revenues of between $180 million to $210 million for full-year 2020, representing significant growth over 2019. Our revenue growth and improvement in profitability also increased our operating cash flows, as shown by the growth of our total cash and investments for the second straight quarter. Having achieved all of our key clinical, regulatory and financial goals in 2019, 2020 looks poised to be one of our most significant value-creating years to date."

(1) 2020 GAAP Net Income guidance does not reflect the potential impact on non-cash GAAP income tax associated with the tax effects of potential intra-entity intangible asset transfers between BioMarin entities as a result of changing international tax laws. Any such changes, if implemented, are not expected to have an impact on operations or cash flows in 2020 but may have an impact on GAAP Net Income in the form of an income tax benefit of potentially greater than $500 million.

(2) All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP Income/Loss. Refer to Non-GAAP Information beginning on page 10 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.
Key Program Highlights
•Valoctocogene roxaparvovec gene therapy for severe hemophilia A: On February 20, 2020, FDA accepted for Priority Review the Biologics License Application (BLA) for valoctocogene roxaparvovec. The Prescription Drug User Fee Act (PDUFA), or target action date for the BLA, has been set for August 21, 2020. On December 23, 2019, the Company announced that the European Medicines Agency (EMA) validated the Company’s Marketing Authorization Application (MAA) for valoctocogene roxaparvovec which has been in

review under accelerated assessment since January. The submissions are based on the Phase 3 interim analysis and the updated three-year Phase 1/2 data of patients treated with valoctocogene roxaparvovec. Both submissions represent the first time a gene therapy product for any type of hemophilia indication is under review for marketing authorization by health authorities.

BioMarin has dosed 134 study participants in the full GENEr8-1 Phase 3 study with 52-week results expected in the first quarter of 2021. Although the trial is open label, BioMarin has implemented a data access plan designed to substantially mirror a blinded trial. This restricts the release of any ongoing data to a small group of medical personnel monitoring and managing the trial, and then, only to the extent necessary to perform their monitoring responsibilities.

BioMarin intends to provide a 4 year update with the 6e13 vg/kg dose subjects and a 3 year update with the 4e13 vg/kg dose subjects from the ongoing Phase 2 study in mid-2020.
•Palynziq for PKU: Palynziq, an injection to reduce blood phenylalanine (Phe) concentrations in adult patients with PKU, was added to BioMarin’s commercial product portfolio upon its U.S. approval May 2018. As of December 31, 2019, 762 patients were on reimbursed Palynziq, with an additional 143 naïve patients enrolled and awaiting their first treatment with commercial Palynziq. Of the 762 patients on therapy at the end of the fourth quarter, 625 were formerly naïve patients and 137 had transitioned from clinical studies. 143 enrolled naive patients were awaiting their first administration of Palynziq as of the end of the fourth quarter. Of the 125 PKU clinics in the U.S., 97 sites had active patients currently on therapy as of December 31, 2019.

On May 6, 2019, the EC granted marketing authorization for Palynziq at doses of up to 60 milligrams once daily, to reduce blood Phe concentrations in patients with PKU aged 16 and older, who have inadequate blood Phe control (blood Phe levels greater than 600 micromol/L) despite prior management with available treatment options. The Company is in the process of securing reimbursement on a country-by-country basis across the European Union and anticipates meaningful revenue contributions from this region in 2020.

•Vosoritide for children with achondroplasia: On December 16, 2019, the Company reported positive final results from its randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of vosoritide. The placebo-adjusted increased change from baseline in growth velocity after one year of treatment with vosoritide, the primary endpoint, was 1.6 cm/yr (p<0.0001). Vosoritide is an investigational, once daily injection analog of C-type Natriuretic Peptide (CNP). The study enrolled 121 children aged 5 to 14 with achondroplasia, the most common form of disproportionate short stature. The results were consistent across the broad patient population studied. Vosoritide was generally well tolerated with no clinically significant blood pressure decreases. Based on these results, the Company plans to meet with health authorities in the first half of 2020 to discuss plans for submitting marketing applications later this year.

On November 14, 2019, the Company provided an update on the ongoing Phase 2 study of vosoritide which demonstrated over 54 months that children in cohort 3 (N=10) of the study, at a dose of 15 µg/kg/day, achieved a statistically significant (p< 0.005) cumulative mean additional height gain of 9.0 cm compared to children, matched for age and gender, in a new comprehensive natural history achondroplasia dataset (N=619). 2.2 cm of this additional increase occurred in the last 12 months further informing our understanding of vosoritide’s ongoing treatment impact. These data are expected to corroborate maintenance of effect at the time of anticipated marketing application submissions later this year.

The vosoritide development program includes four distinct areas of focus to support global approval. In addition to the completed Phase 3 study and ongoing Phase 2 study in children ages 5-14 years, the global program includes a large contemporaneous natural history study which is underway.
The fourth component of the Company’s global development program with vosoritide, includes a large Phase 2 study in infants and young children (newborn to 60 months old) with achondroplasia, to determine the impact of treatment in this age group. Cohorts 1 and 2 include children from ages 6 months through 5 years of age, is near enrollment completion. Cohort 3, includes children ages 0 to 6 months old and, is actively enrolling.
•BMN 307 gene therapy product candidate for phenylketonuria (PKU): On January 13, 2020 the Company announced that both the FDA and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the

U.K. have granted the Company Investigational New Drug (IND) status and approved its Clinical Trial Application (CTA), respectively, for BMN 307.

The Company expects to start dosing patients in PHEARLESS, a Phase 1/2 study, in the first quarter of 2020 with product made at commercial scale from its award-winning gene therapy manufacturing facility. Both the FDA and EMA have granted BMN 307 Orphan Status.
Preclinical data with BMN 307 demonstrated a lifetime Phe correction sustained at 80 weeks in mouse models. BMN 307 is an AAV vector containing the DNA sequence that codes for the phenylalanine hydroxylase enzyme that is deficient in people with PKU.

•BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): On November 14, 2019, the Company introduced its third gene therapy candidate, BMN 331, for the treatment of Hereditary Angioedema (HAE). BioMarin plans to build on its ever wider and deeper experience in developing gene therapies for severe hemophilia A and PKU to improve efficiencies in the development process, and optimize capsid and transgene design. The Company expects to begin IND-enabling studies in early to mid-2020.

•Vosoritide for the treatment of Dominantly Inherited Short Stature (DISS): On November 14, 2019, the Company announced that vosoritide will be studied in broader genetic statural abnormalities starting with dominantly inherited short stature (DISS), as part of a research collaboration with Children’s National Hospital. The Company plans to build on its learnings with vosoritide in achondroplasia and look for efficiencies in the development process, particularly around pre-clinical research and manufacturing. The Company expects the trial with vosoritide for DISS to begin mid-2020.

•Gene Therapy manufacturing productivity increases capacity: On January 13, 2020, the Company announced that significant improvements in productivity in the gene therapy facility had increased capacity for up to 10,000 patients per year, depending on dose and product mix.
BioMarin will host a conference call and webcast to discuss fourth quarter and full year 2019 financial results and 2020 guidance today, Wednesday, February 26, 2020 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 Replay Dial-in Number: 855.859.2056 International Dial-in Number: 574.990.1362
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Conference ID: 9967337
Conference ID: 9967337