On March 1, 2021 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and genetically defined diseases, reported that it has submitted a Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for TIBSOVO (ivosidenib tablets) as a potential treatment for patients with previously treated isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (Press release, Agios Pharmaceuticals, MAR 1, 2021, View Source [SID1234575810]). Agios has requested priority review for the application, which, if granted, could result in a six-month review process.

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"Cholangiocarcinoma is a rare, aggressive cancer with limited effective therapies, and patients are in desperate need of new treatment options – particularly those who experience disease progression after chemotherapy," said Chris Bowden, M.D., chief medical officer at Agios. "We are proud of the work we have done on behalf of these patients and look forward to working closely with the FDA during the review of the first oral therapy targeting an IDH1 mutation for patients with previously treated IDH1-mutated cholangiocarcinoma."

The sNDA submission is supported by data from the ClarIDHy study, the first and only randomized Phase 3 trial for previously treated IDH1-mutated cholangiocarcinoma. Data from the study were previously presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper), held in September 2019 in Barcelona, Spain, and published in The Lancet Oncology on May 13, 2020. A final analysis of the data was featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) on January 17, 2021.

About Cholangiocarcinoma
Cholangiocarcinoma is a rare, aggressive cancer of the bile ducts within and outside of the liver. IDH1 mutations occur in approximately 13% of cholangiocarcinoma cases and are not associated with prognosis. There are no approved systemic therapies for IDH1-mutated cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed advanced or metastatic disease.

About TIBSOVO (ivosidenib tablets)
TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult patients with relapsed or refractory AML.
IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of AML patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.
Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.
Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.
QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION
Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

On March 1, 2021 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biopharmaceutical company creating a new class of drugs based on targeted protein degradation, reported financial results for the fourth quarter and full year ended December 31, 2020 and provided a corporate update (Press release, Arvinas, MAR 1, 2021, View Source [SID1234575838]).

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"2020 was a breakthrough year for Arvinas and for the patients we aim to serve, as we reported clear signals of efficacy in both of our clinical-stage programs. These data provided further validation that our approach to protein degradation could potentially change the lives of patients with few or no therapeutic options," said John Houston, Ph.D., Chief Executive Officer at Arvinas. "Despite the unprecedented circumstances of a pandemic, our clinical trials and preclinical research continued to deliver, and we enter 2021 well positioned to extend our success and progress our programs in oncology and neurodegeneration."

Business Highlights and Recent Developments

Presented interim Phase 1 data for ARV-471 showing potential for best-in-class safety and tolerability, estrogen receptor (ER) degradation greater than that previously reported for the current standard of care agent (fulvestrant), and a robust efficacy signal in heavily pretreated patients with locally advanced or metastatic ER positive / HER2 negative (ER+/HER2-) breast cancer
Presented data from the ongoing dose escalation portion of the Phase 1/2 trial of ARV-110 in men with metastatic castration-resistant prostate cancer (mCRPC), providing additional evidence of anti-tumor activity and patient benefit, including a prostate specific antigen reduction ≥50% (PSA50) in 2 of 5 (40%) in a molecularly defined patient population
Closed an underwritten public offering of 6,571,428 shares of common stock at a public offering price of $70.00 per share, including the exercise in full by the underwriters of their option to purchase additional shares of common stock. Arvinas received net proceeds of $431.9 million, after deducting underwriting discounts and commissions and offering expenses
Initiated the ARDENT Phase 2 dose expansion study of ARV-110 (Dose: 420 mg daily)
Initiated the VERITAC Phase 2 dose expansion study of ARV-471 (Dose: 200 mg daily)
Initiated a Phase 1b trial of ARV-471 in combination with Ibrance (palbociclib)
Anticipated Milestones and Expectations

ARV-471

Completion of the Phase 1 dose escalation (1H21)
Presentation of completed Phase 1 dose escalation data (2H21)
Announcement of safety data from the Phase 1b trial in combination with Ibrance (palbociclib) (2H21)
Initiation of a window of opportunity study in adjuvant breast cancer (2H21)
Initiation of a combination trial of ARV-471 and another targeted therapy in 2L/3L metastatic breast cancer (2H21)
ARV-110

Completion of the Phase 1 dose escalation (1H21)
Presentation of completed Phase 1 dose escalation data (2H21)
Announcement of interim data from the ARDENT Phase 2 dose expansion at 420 mg (2H21)
Initiation of combination trial(s) with standards-of-care (2021)
Other Clinical Milestones

Initiation of first-in-human study of ARV-766, an androgen receptor (AR) degrader with a differentiated profile from ARV-110, in patients with metastatic castration-resistant prostate cancer (1H21)
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities will be sufficient to fund its planned operating expenses and capital expenditures into 2024.

Full Year and Fourth Quarter Financial Results

Cash, Cash Equivalents and Marketable Securities Position: As of December 31, 2020, cash, cash equivalents and marketable securities were $688.5 million as compared with $280.9 million as of December 31, 2019. The increase primarily related to net proceeds from the issuance of common stock and proceeds from the exercise of stock options of $504.7 million, proceeds from two collaborators of $7.4 million, partially offset by cash used to fund operations of approximately $98.1 million and cash used to purchase fixed assets and leasehold improvements of $6.4 million.

Research and Development Expenses: Research and development expenses were $108.4 million and $33.2 million for the year and quarter ended December 31, 2020, respectively, as compared with $67.2 million and $20.4 million for the year and quarter ended December 31, 2019, respectively. The increase in research and development expenses for the year of $41.2 million primarily related to Arvinas’ continued investment in its wholly owned platform, exploratory and lead optimization programs of $17.6 million, its androgen receptor (AR) program of $12.3 million and estrogen receptor program (ER) of $11.3 million. The increase in research and development expense for the quarter of $12.8 million primarily related to Arvinas’ continued investment in its wholly owned platform, exploratory and lead optimization programs of $5.1 million, its AR program of $4.8 million and ER program of $2.9 million.

General and Administrative Expenses: General and administrative expenses were $38.3 million and $12.2 million for the year and quarter ended December 31, 2020, respectively, as compared with $27.3 million and $7.3 million for the year and quarter ended December 31, 2019, respectively. The increase in general and administrative expenses for the year of $11.0 million related to an increase of $9.6 million in personnel and facility related costs, including $4.8 million related to stock compensation expense, and insurance, taxes and professional fees of $1.4 million. The increase in general and administrative expenses for the quarter of $5.0 million primarily related to an increase of $2.9 in personnel and facility cost, including $1.4 million related to stock compensation expense and $1.7 million of legal and other professional services.

Revenues: Revenues were $21.8 million and $2.2 million for the year and quarter ended December 31, 2020, respectively, as compared with $43.0 million and $4.9 million for the year and quarter ended December 31, 2019, respectively. Revenue for the year ended December 31, 2019 included $24.7 million of revenue recognized from the Arvinas contribution of the license to the joint venture between Bayer and Arvinas to pursue the PROTAC technology in agricultural applications (the Joint Venture). The remaining collaboration revenue of $18.3 million and revenue of $4.9 million for the year and quarter ended December 31, 2019, respectively, was generated from the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017. The increase in collaboration revenue of $3.5 million for the year was primarily related to the Bayer agreement having only a partial year of revenue recognized in 2019 and an increase in activities related to the Pfizer agreement. The decrease in collaboration revenue of $2.7 million in the quarter primarily related to a collaborator adding new targets that extended the period of revenue recognition for the collaboration agreement.

Loss from Equity Method Investment: Loss from equity method investment for the year ended December 31, 2019 was $24.7 million, which related to the loss from the equity method investment in the Joint Venture. The loss was generated from the Joint Venture’s expensing the values associated with the contributed intellectual property from the Joint Venture partners.

Net Loss: Net loss was $119.3 million and $41.5 million for the year and quarter ended December 31, 2020, respectively, as compared with $70.3 million and $21.0 million for the year and quarter ended December 31, 2019, respectively. The increase in net loss for the year and quarter ended December 31, 2020 of $49.0 million and $20.5 million, respectively, primarily related to Arvinas’ continued investment in its platform, exploratory and lead optimization programs, its AR program, its ER program, and an increase in general and administrative infrastructure costs.

About ARV-110
ARV-110 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor.

On March 1, 2021 MannKind Corporation (NASDAQ:MNKD) reported that it intends to offer, subject to market conditions and other factors, $150.0 million aggregate principal amount of Convertible Senior Notes due 2026 (the "notes") in a private placement (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Mannkind, MAR 1, 2021, View Source [SID1234575856]). MannKind also intends to grant the initial purchasers of the notes an option to purchase, within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $22.5 million aggregate principal amount of notes.

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The notes will be general unsecured obligations of MannKind and will accrue interest payable semiannually in arrears. Upon conversion, MannKind will pay or deliver, as the case may be, cash, shares of MannKind’s common stock or a combination of cash and shares of MannKind’s common stock, at its election. The interest rate, initial conversion rate and other terms of the notes will be determined at the time of pricing of the offering.

MannKind intends to use the net proceeds from this offering for working capital and other general corporate purposes, including a Phase 3 clinical trial of Afrezza in pediatric subjects and further development of product candidates in MannKind’s pipeline. MannKind may use a portion of the proceeds from this offering to pay down a portion of existing debt or for acquisitions or strategic investments in complementary businesses or technologies, although MannKind does not currently have any plans for any such debt repayment, acquisitions or investments.

The notes and any shares of MannKind’s common stock issuable upon conversion of the notes have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any such state or jurisdiction.

On March 1, 2021 NanoString Technologies, Inc. (NASDAQ:NSTG), a leading provider of life science tools for discovery and translational research, reported financial results for the fourth quarter and year ended December 31, 2020 (Press release, NanoString Technologies, MAR 1, 2021, View Source [SID1234575872]).

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Fourth Quarter Financial Highlights

Product and service revenue of $35.7 million, 6% year-over-year growth. On a pro forma basis, reflecting the impact of the Veracyte transaction on revenue recorded for Prosigna IVD kits, product and service revenue increased by 9%
Instrument revenue of $15.3 million, 11% year-over-year growth. Instrument revenue includes $9.3 million of GeoMx Digital Spatial Profiler (DSP) instrument revenue
Consumables revenue of $16.6 million, 2% year-over-year decline. On a pro forma basis, reflecting the impact of the Veracyte transaction, consumables revenue increased by 3%. Consumables revenue includes $2.8 million of GeoMx DSP consumables revenue
Service revenue of $3.8 million, 29% year-over-year growth
Full Year 2020 Financial Highlights

Product and service revenue of $111.4 million, 7% year-over-year growth. Pro forma growth was 14%
Instrument revenue of $47.8 million, 54% year-over-year growth. Instrument revenue includes $29.6 million of GeoMx DSP instrument revenue
Consumables revenue of $50.1 million, 18% year-over-year decline. On a pro forma basis, consumables revenue decreased 10%. Consumables revenue includes $5.3 million of GeoMx DSP consumables revenue
Service revenue of $13.5 million, 16% year-over-year growth
Cash, cash equivalents and short-term investments balance of $440.7 million
"During 2020, we successfully achieved all of our strategic objectives against the challenging operating backdrop of the COVID-19 pandemic. We extended our leadership in spatial biology, growing GeoMx DSP instrument orders by 50% and opening up a large market opportunity in basic discovery through the introduction of the first next generation sequencing panels for GeoMx," said Brad Gray, president and CEO of NanoString. "We look forward to continuing our momentum in 2021, with key catalysts including the commercial launch of our GeoMx Whole Transcriptome Atlas and a Technology Access Program service for our recently unveiled Spatial Molecular Imager."

Recent Business Highlights

Nature Methods 2020 "Method of the Year": Leading scientific journal Nature Methods announced that spatially resolved transcriptomics was selected as their 2020 "Method of the Year"
Spatial Genomics Summit: Held third annual Spatial Genomics Summit on February 23rd, focused on scientific advancements and new technology in the spatial genomics market. Panelists included leading researchers from Bristol-Myers Squibb, Harvard Medical School, Wellcome Sanger Trust and the Fred Hutchinson Cancer Research Center
Advances in Genome Biology and Technology (AGBT) Conference: Hosted Gold Sponsorship Workshop focused on "Progressing Spatial Biology from Tissue Architecture to Sub-cellular Functions." AGBT included more than 20 posters and presentations on spatial biology using GeoMx DSP and our Spatial Molecular Imager
GeoMx DSP

GeoMx Shipments and Installations: Shipped approximately 40 and installed approximately 30 GeoMx DSP instruments in the fourth quarter, bringing cumulative shipments to more than 160 and cumulative installs to approximately 130 instruments since launch
Launch of Whole Transcriptome Atlas: Announced the commercial availability of the GeoMx Whole Transcriptome Atlas, which provides expanded access to next generation sequencing (NGS) readout on GeoMx DSP
Continued Growth of GeoMx Technology Access Program (TAP): Generated a record of 87 new GeoMx TAP project orders in the fourth quarter, of which more than 40% used our Whole Transcriptome Atlas with NGS readout. As of December 31, 2020, we have conducted over 430 TAP projects for approximately 200 customers
Publications: Continued growth of peer-reviewed publications utilizing GeoMx DSP technology, with 6 new publications in the fourth quarter, bringing the cumulative total to 35 peer-reviewed publications as of December 31, 2020
Spatial Molecular Imager

Unveiled Spatial Molecular Imaging Platform: Announced the development of the Spatial Molecular Imager, a new spatial biology platform capable of measuring the expression of 1,000+ genes at single-cell and sub-cellular resolution
Launch of Spatial Molecular Imager under TAP: Announced a new SMI TAP service offering, providing the opportunity for customers to access the capabilities of SMI in 2021 by sending their biological samples to our Seattle, WA facility to be analyzed
nCounter

nCounter Installed Base: Grew installed base to approximately 950 nCounter Analysis Systems at December 31, 2020, representing 13% growth over the prior year
Publications: Surpassed 4,000 cumulative peer-reviewed publications utilizing nCounter technology, representing continued research momentum for the nCounter platform
Fourth Quarter Financial Results

We have elected to present selected non-GAAP, or adjusted, financial measures, including Adjusted EBITDA. These adjusted financial measures are calculated excluding certain items that may make it more challenging to compare our GAAP operating results across periods. Such items may include collaboration revenue, stock-based compensation, depreciation and amortization, or one-time charges such as transaction related fees and expenses or restructuring charges and severance costs. A reconciliation of adjusted financial measures to the nearest comparable GAAP financial measure can be found in the notes and table at the end of this press release.

2021 Outlook

The company, based on its plans and initiatives for 2021, expects to record results approximately as follows:

Total product and service revenue of $140 to $150 million, representing growth of 26% to 35% as compared to 2020
GeoMx DSP revenue of $45 to $50 million
nCounter revenue, inclusive of all service revenue, of $95 to $100 million
Adjusted gross margin on product and service revenue of 55% to 57%
Adjusted operating expenses of $145 to $155 million
Adjusted EBITDA loss of $65 to $70 million
Supplemental Information

As a supplement to the table above, we have posted to the investor relations section of our website, at www.nanostring.com, supplemental financial data that includes our adjusted financial measures as compared to the nearest comparable GAAP financial measures, for the fourth quarter and the full year of 2020 and for each quarter and the full year of 2019.

Conference Call

Management will host a conference call today beginning at 1:30 pm PT / 4:30 pm ET to discuss these results and answer questions. Investors and other interested parties can register for the call in advance by visiting View Source After registering, an email confirmation will be sent, including dial-in details and unique conference call codes for entry. Registration is open throughout the call but to ensure connection for the full call, registration in advance is recommended. The link to the webcast and audio replay will be made available at the Investor Relations website: www.nanostring.com. A replay of the call will be available beginning March 1, 2021 at 7:30pm ET through midnight ET on March 8, 2021. To access the replay, dial (800) 585-8367 or (416) 621-4642 and reference Conference ID: 3093307. The webcast will also be available on our website for one year following the completion of the call.

Non-GAAP, or Adjusted, Financial Information

We believe that the presentation of non-GAAP, or adjusted, financial information provides important supplemental information to management and investors regarding financial and business trends relating to our financial condition and results of operations. Reconciliation of adjusted financial measures to the most directly comparable financial result as determined in accordance with GAAP are included at the end of this press release following the accompanying financial data. A reconciliation of adjusted guidance measures to corresponding GAAP measures is not available on a forward-looking basis without unreasonable effort due to the uncertainty regarding certain expenses that may be incurred in the future. For further information regarding why we believe that these adjusted measures provide useful information to investors, the specific manner in which management uses these measures and some of the limitations associated with the use of these measures, please refer to "Notes Regarding Non-GAAP Financial Information" at the end of this press release.

Pro Forma Financial Information

As used in this press release, "pro forma" percentages are calculated by comparing the applicable period-over-period financial results to reflect the impact of the Veracyte transaction as if such transaction had occurred on January 1, 2019, the beginning of the earliest period presented. Further disclosure regarding the terms and pro forma impact of the Veracyte transaction can be obtained in our Current Report on Form 8-K filed with the Securities and Exchange Commission on December 4, 2019.

On March 1, 2021 Invest Puerto Rico (InvestPR), the Island’s economic development organization, and the Puerto Rico Department of Economic Development and Commerce (DDEC), reported that CytoImmune Therapeutics Puerto Rico LLC ("CTPR") will establish cell therapy operations in Puerto Rico in 2021 with the aim of developing novel, coordinate immunotherapy solutions for cancer patients (Press release, CytoImmune Therapeutics, MAR 1, 2021, View Source [SID1234575897]).

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The new company, an affiliate of the California-based CytoImmune Therapeutics, organized under the provisions established by the Puerto Rico Incentives Code (Act 60) will be the first of its kind on the Island. Its purpose is to conduct R&D and manufacturing in a 37,000 square foot facility in Toa Baja.

CytoImmune has been developing and commercializing novel cancer immunotherapy products designed to utilize the power of the patient’s own immune system to eliminate cancer cells. This happens through proprietary Chimeric Antigen Receptor (CAR) engineered T cells (CAR-T) technology, and an approach for natural killer (NK) cell immunotherapy that involves a CAR NK cell. This technology enables the cell to recognize specific proteins or antigens present on the surface of tumor cells.

Now, manufacturing of CAR NK cells for first-inhuman phase 1 clinical trials will be performed in CytoImmune’s Puerto Rico facilities. Because of the ability to freeze and thaw these CAR NK cells, multiple institutions can be involved in early phase clinical trials, including some in Puerto Rico, thereby hastening accrual in each clinical stage.

The initiative represents an investment of $28 million in the Island ($8 million by CTPR with co-investment of $17 million by CytoImmune), including machinery and equipment. CTPR expects to hire up to 100 professionals with estimated total payroll of $7 million annually.

"We are pleased to welcome CytoImmune to Puerto Rico. The company’s commitment to stand up R&D and manufacturing facilities on the Island is a testament to Puerto Rico’s potential as a viable investment destination and speaks to Puerto Rico’s value proposition as a life science hub," says Rodrick Miller, CEO of Invest Puerto Rico. "We work to strengthen Puerto Rico’s position each day with an ever-resilient business ecosystem designed to encourage new investment in the short and long term."

"CytoImmune Therapeutics Puerto Rico is a leader in the field of cell therapy and immunotherapy for the treatment of cancers. This is an excellent opportunity to establish an R&D facility in Toa Baja. CTPR with this remarkable scientific discovery will bring hope to many of the sick people with cancer worldwide," says Bernardo Márquez García, the mayor of Toa Baja. "We understand that our Municipality and Puerto Rico can benefit from 100+ jobs, and my administration will support CytoImmune’s development."

Will Rosellini, Co-founder and President of CytoImmune, noted, "Puerto Rico was the obvious choice for expanding our operations. The Island, with proven history in the life science sector, can support our research and development, including a deep talent pool, supportive business climate, and many other high-value intangibles."