On February 4, 2021 Hoffmann-La Roche reported that solid results in 2020 (Press release, Hoffmann-La Roche, FEB 4, 2021, View Source [SID1234574595])

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Group sales increase 1%1 at constant exchange rates (CER); 5% decline in Swiss francs, as a result of continued appreciation of the Swiss franc against most currencies

Pharmaceuticals Division sales decline 2%; continued strong sales growth of newly launched medicines (+32%2, including Tecentriq, Hemlibra, Ocrevus, Perjeta and Kadcyla) largely offsets the impact of competition from biosimilars (CHF -5.1 billion at CER3), but not the additional COVID-19-related impact from missed medical appointments
Diagnostics Division sales grow 14% for the full year (+28% in the fourth quarter) due to COVID-19 diagnostics; more than offsetting a decline in routine testing due to COVID-19
Roche’s contributions to the fight against the COVID-19 pandemic:
Launch of 15 new diagnostic solutions for COVID-19

Key tests launched in the fourth quarter:
USA: Elecsys Anti-SARS-CoV-2 S antibody test, which can play a critical role in measuring a person’s vaccine-induced immune response
Europe: Elecsys SARS-CoV-2 Antigen test to support high-volume testing of suspected COVID-19 patients
Production capacity for SARS-CoV-2 tests and COVID-19-related medicines ramped up significantly at unprecedented speed; substantial funds committed to further expand supply chain capacities (>CHF 800 million)
Major partnerships: With Regeneron to increase global supply of investigational antiviral antibody combination (August), with Atea to develop a potential oral COVID-19 treatment (October), and with Moderna to include our recently launched antibody test in their ongoing vaccine trials (December)

Approvals for medicines in the fourth quarter:
USA: Gavreto (thyroid cancer); Xofluza (influenza); Xolair (nasal polyps)
Europe: Tecentriq plus Avastin (liver cancer), Phesgo (breast cancer), Xofluza (influenza)4
Strong pipeline: record number of 19 new compounds in phase III trials or filed for approval; investment in research and development further increased by 8% to CHF 12.2 billion
Core earnings per share (EPS) grow ahead of sales at 4% (-5% in CHF)
IFRS net income of CHF 15.1 billion, increasing 17% (7% in CHF), mainly due to the lower goodwill write-offs compared to the previous year
Board proposes dividend to increase to CHF 9.10. Subject to shareholder approval, this would be the 34th consecutive dividend increase)
Outlook for 2021: Despite the continued strong impact of biosimilars, sales are expected to grow in the low- to mid-single digit range, at constant exchange rates. Core earnings per share are targeted to grow broadly in line with sales, at constant exchange rates. Roche expects to increase its dividend in Swiss francs further.

Commenting on the Group’s results, Roche CEO Severin Schwan said: "Roche continues to make important contributions to fighting the COVID-19 pandemic. We developed in record time a comprehensive portfolio of diagnostic solutions and entered new partnerships to develop and produce effective COVID-19 medicines. The demand for our new medicines which benefit people living with serious conditions, such as cancer, multiple sclerosis, haemophilia and spinal muscular atrophy, remains high. Based on our rejuvenated portfolio and the significant progress made in developing our product pipeline, Roche is strongly positioned for future growth."

Group results
In 2020, Group sales rose 1% (-5% in CHF) to CHF 58.3 billion. The core operating profit increased 4% (-4% in CHF), reflecting the underlying business performance, and core EPS grew 4% (-5% in CHF), ahead of sales. The appreciation of the Swiss franc against almost all currencies had a significant adverse net impact on the results expressed in Swiss francs compared to constant exchange rates.

The IFRS net income increased 17% (7% in CHF). This increase is mainly due to the lower goodwill write-offs compared to the previous year.

Sales in the Pharmaceuticals Division decreased 2% to CHF 44.5 billion, mainly due to stronger than expected biosimilars competition and the COVID-19 pandemic. The new medicines (launched since 2012) continued their strong growth (+32%, or +CHF 4.7 billion). In 2020, they generated sales of CHF 18.4 billion, thus already contributing more than 40% to the division’s total sales.

While sales of the new medicines grew strongly, the impact of the competition from biosimilars for the established medicines Herceptin, Avastin and MabThera/Rituxan was significant, with an estimated combined CHF 5.1 billion of sales reduction in the US, Europe and Japan.

On February 4, 2021 Bristol-Myers Squibb Company (NYSE:BMY) ("Bristol Myers Squibb"), with its wholly-owned subsidiary Celgene Corporation ("Celgene") (collectively, the "Offerors"), reported the commencement of 20 separate offers to purchase for cash notes issued by the Offerors listed in the tables below (collectively, the "Notes") for an aggregate purchase price of up to $4.0 billion (Press release, Bristol-Myers Squibb, FEB 4, 2021, View Source [SID1234574616]).

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The Total Consideration (as defined below) for each series of Notes will be based on the fixed spread for the applicable series of Notes plus the yield of the specified Reference U.S. Treasury Security for that series as of 11:00 a.m. (New York City time) on February 19, 2021, unless extended with respect to any Offer (as defined below) (such date and time with respect to an Offer, as the same may be extended with respect to such Offer, the "Price Determination Date"). The Total Consideration does not include the applicable Accrued Coupon Payment (as defined below), which will be payable in cash in addition to the applicable Total Consideration. For the avoidance of doubt, the Early Tender Premium is included in the Total Consideration calculated based on the fixed spread for the applicable series of Notes and is not in addition to the Total Consideration.

Payable, as part of the applicable Total Consideration, per each $1,000 principal amount of the specified series of Notes validly tendered at or prior to the applicable Early Tender Deadline (as defined below) and accepted for purchase (the "Early Tender Premium"). The total consideration for each $1,000 principal amount of each series of Notes validly tendered at or prior to the applicable Early Tender Deadline (including the Early Tender Premium) is referred to as the "Total Consideration" for such series. Holders of Notes (each, a "Holder" and collectively, "Holders") who validly tender Notes of a series after the applicable Early Tender Deadline, but at or prior to the applicable Expiration Date (as defined below), will receive the tender consideration for any such series accepted for purchase by the applicable Offeror, which is equal to the Total Consideration minus the Early Tender Premium (with respect to such series, the "Tender Consideration").

Denotes a series of Notes for which the Total Consideration and the Tender Consideration will be determined taking into account the par call date, instead of the maturity date, of the Notes of such series in accordance with standard market practice.

The outstanding debt securities listed in (i) the first table above labeled "2023 Pool" are referred to collectively as the "2023 Pool Notes," (ii) the second table above labeled "2024 Pool" are referred to collectively as the "2024 Pool Notes," (iii) the third table above labeled "2025 Pool" are referred to collectively as the "2025 Pool Notes," and (iv) the fourth table above labeled "High Coupon Pool" are referred to collectively as the "High Coupon Pool Notes." The High Coupon Pool Notes, the 2023 Pool Notes, the 2024 Pool Notes and the 2025 Pool Notes are referred to collectively as the "Notes," and each series of Notes is referred to as a "series." We refer to each offer to purchase a series of Notes for cash as an "Offer," the offers to purchase the 2023 Pool Notes collectively as the "2023 Pool Offers," the offers to purchase the 2024 Pool Notes collectively as the "2024 Pool Offers," the offers to purchase the 2025 Pool Notes collectively as the "2025 Pool Offers," the offers to purchase the High Coupon Pool Notes collectively as the "High Coupon Pool Offers," and all the offers to purchase Notes are referred to collectively as the "Offers."

The Offers are subject to the terms and conditions described in the Offer to Purchase dated February 4, 2021 (as it may be amended or supplemented from time to time, the "Offer to Purchase") which sets forth a detailed description of the Offers, including (i) the Acceptance Priority Procedures (as described below), (ii) a $950 million maximum aggregate purchase price of the 2023 Pool Notes validly tendered in the 2023 Pool Offers, excluding the applicable Accrued Coupon Payments (the "2023 Pool Maximum"), (iii) a $1.5 billion maximum aggregate purchase price of the 2024 Pool Notes validly tendered in the 2024 Pool Offers, excluding the applicable Accrued Coupon Payments (the "2024 Pool Maximum"), (iv) a $650 million maximum aggregate purchase price of the 2025 Pool Notes validly tendered in the 2025 Pool Offers, excluding the applicable Accrued Coupon Payments (the "2025 Pool Maximum"), and (v) a $900 million maximum aggregate purchase price of the High Coupon Pool Notes validly tendered in the High Coupon Pool Offers, excluding the applicable Accrued Coupon Payments (the "High Coupon Pool Maximum").

The primary purpose of the Offers is to acquire the maximum principal amount of 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes and High Coupon Pool Notes in the designated priority order for which the aggregate purchase price (excluding the applicable Accrued Coupon Payments) for each such group of Notes does not exceed the 2023 Pool Maximum, the 2024 Pool Maximum, the 2025 Pool Maximum and the High Coupon Pool Maximum, respectively. The Offers are not conditioned on any minimum amount of Notes being tendered, and none of the Offers are conditioned on the consummation of the other Offers. The Offers are subject to certain other general conditions as described in the Offer to Purchase. Each Offer may be amended, extended or, upon failure of a condition to be satisfied or waived prior to the applicable Early Tender Deadline (for any Offers for which the Offerors elect to exercise their Early Settlement Right (as defined below)) or the applicable Expiration Date (for any Notes not settled on the Early Settlement Date), terminated individually.

The Offers will each expire at 11:59 p.m. (New York City time) on March 4, 2021, unless extended or earlier terminated by the Offerors (such date and time with respect to an Offer, as the same may be extended with respect to such Offer, the "Expiration Date"). To be eligible to receive the Total Consideration, which includes the Early Tender Premium, Holders must validly tender their Notes at or prior to 5:00 p.m. (New York City time) on February 18, 2021, unless extended (such date and time with respect to an Offer, as the same may be extended with respect to such Offer, the "Early Tender Deadline"). Holders who validly tender their Notes after the applicable Early Tender Deadline, but at or prior to the applicable Expiration Date, will be eligible to receive the Tender Consideration for any such series accepted for purchase. All Holders whose Notes are accepted in an Offer will receive a cash payment equal to accrued and unpaid interest on such Notes to, but not including, the relevant Settlement Date (as defined below) (the "Accrued Coupon Payment") in addition to their Total Consideration or Tender Consideration, as applicable.

Notes may be validly withdrawn at any time at or prior to 5:00 p.m. (New York City time) on February 18, 2021, (such date and time with respect to an Offer, as the same may be extended with respect to such Offer), but not thereafter, unless extended with respect to any Offer. Holders should not tender any Notes that they do not wish to be accepted for purchase.
Subject to the satisfaction or waiver of the conditions of the Offers, the Acceptance Priority Procedures will operate concurrently, but separately, for the 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes and High Coupon Pool Notes, in each case subject to proration as described in the Offer to Purchase.
On the terms and subject to the conditions set forth in the Offer to Purchase, the Offerors are offering to purchase the following outstanding securities issued by it for the consideration described below:

Subject to the satisfaction or waiver of the conditions of the Offers, the "Acceptance Priority Procedures" will operate concurrently, but separately, for the (i) 2023 Pool Offers, (ii) 2024 Pool Offers, (iii) 2025 Pool Offers, and (iv) High Coupon Pool Offers, in each case, as follows:

first, if the aggregate cash purchase price (excluding the applicable Accrued Coupon Payments) of all 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes or High Coupon Pool Notes, as applicable, validly tendered at or prior to the applicable Early Tender Deadline by Holders does not exceed the applicable pool maximum, then the applicable Offeror will accept all such Notes. However, if the aggregate cash purchase price (excluding the applicable Accrued Coupon Payments) of all 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes or High Coupon Pool Notes, as applicable, validly tendered at or prior to the applicable Early Tender Deadline by Holders exceeds the applicable pool maximum, then the Offerors will (i) accept such Notes for purchase for cash, starting at the highest acceptance priority level (level 1) and, if there is more than one priority level, moving sequentially to each lower acceptance priority level (the lowest of which is level 2 in the case of the 2023 Pool Offers and 2024 Pool Offers and level 8 in the case of the High Coupon Pool Offers; the 2025 Pool Offers have only one priority level), until the aggregate cash purchase price (excluding the applicable Accrued Coupon Payments) of such Notes equals the applicable pool maximum, (ii) prorate the series of such Notes with the lowest acceptance priority level accepted for purchase for cash (including equal proration between Notes having the same priority but different Offerors) and (iii) not accept for purchase for cash (x) any such Notes of a series with an acceptance priority level below the prorated series or (y) any 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes or High Coupon Pool Notes, as applicable, validly tendered after the applicable Early Tender Deadline; and
second, if the applicable pool maximum is not exceeded at the applicable Early Tender Deadline, the Offerors will repeat the steps described in the prior bullet with respect to all 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes or High Coupon Pool Notes, as applicable, validly tendered after the applicable Early Tender Deadline, but at or prior to the applicable Expiration Date, in order to determine the aggregate principal amount of such Notes that the applicable Offeror will accept for purchase in the 2023 Pool Offers, the 2024 Pool Offers, the 2025 Pool Offers or the High Coupon Pool Offers, as applicable.
All 2023 Pool Notes, regardless of acceptance priority level, that are validly tendered at or prior to the applicable Early Tender Deadline will have priority over 2023 Pool Notes validly tendered after the applicable Early Tender Deadline and at or prior to the applicable Expiration Date.
All 2024 Pool Notes, regardless of acceptance priority level, that are validly tendered at or prior to the applicable Early Tender Deadline will have priority over 2024 Pool Notes validly tendered after the applicable Early Tender Deadline and at or prior to the applicable Expiration Date.
All 2025 Pool Notes, regardless of acceptance priority level, that are validly tendered at or prior to the applicable Early Tender Deadline will have priority over 2025 Pool Notes validly tendered after the applicable Early Tender Deadline and at or prior to the applicable Expiration Date.
All High Coupon Pool Notes, regardless of acceptance priority level, that are validly tendered at or prior to the applicable Early Tender Deadline will have priority over High Coupon Pool Notes validly tendered after the applicable Early Tender Deadline and at or prior to the applicable Expiration Date
Provided that all conditions to the 2023 Pool Offers, the 2024 Pool Offers, the 2025 Pool Offers, and/or the High Coupon Pool Offers have been satisfied or waived by the applicable Offeror by the applicable Early Tender Deadline, the Offerors may, but are not obligated to, elect to exercise their right (the "Early Settlement Right"), with respect to the Offers for which the conditions have been satisfied or waived, to settle all Notes validly tendered at or prior to the applicable Early Tender Deadline and accepted for purchase in such Offers (the "Early Settlement Date"). The Early Settlement Date will be determined at the Offerors’ option and is currently expected to occur on the third business day immediately following the Early Tender Deadline. If the Offerors elect to exercise their Early Settlement Right with respect to any 2023 Pool Notes, 2024 Pool Notes, 2025 Pool Notes and/or High Coupon Pool Notes, in each case validly tendered at or prior to the applicable Early Tender Deadline and accepted for purchase, the Offerors will settle all such Notes on the Early Settlement Date. If the Offerors elect to exercise their Early Settlement Right with respect to the 2023 Pool Offers, the 2024 Pool Offers, the 2025 Pool Offers and/or the High Coupon Pool Offers, the Offerors will announce in a press release promptly after the applicable Early Tender Deadline that they are exercising their Early Settlement Right with respect to such Offers. On the Early Settlement Date, all Notes validly tendered at or prior to the applicable Early Tender Deadline and accepted for purchase in the Offers for which the Offerors have elected to exercise their Early Settlement Right will receive the applicable Total Consideration and Accrued Coupon Payment. The "Final Settlement Date," if any, is the date on which the Offerors will settle all Notes validly tendered and accepted for purchase and not previously settled on the Early Settlement Date. The Final Settlement Date is expected to be the second business day following the applicable Expiration Date, unless extended with respect to any Offer. Each of the Early Settlement Date and the Final Settlement Date is referred to as a "Settlement Date."

Promptly after the Price Determination Date, the Offerors will issue a press release specifying, among other things, the Offer Yield and Total Consideration for each series of Notes, the aggregate principal amount of Notes validly tendered at or prior to the applicable Early Tender Deadline and accepted in each Offer and the proration factor (if any) applied to such validly tendered Notes with respect to each Offer.

The Offerors expressly reserve the right, in their sole discretion, subject to compliance with applicable law and regulations, not to purchase any Notes or to extend, amend and/or terminate its respective Offers and to amend or waive any of the terms and conditions of any Offer. Holders are advised to read carefully the Offer to Purchase for full details of and information on the procedures for participating in the Offer, as applicable. If the Offerors terminate any Offer with respect to one or more series of Notes, they will give written notice thereof to the Tender and Information Agent (as defined below) and will make a public announcement thereof as promptly as practicable, and all Notes tendered pursuant to such terminated Offer will be returned promptly to the tendering Holders thereof. With effect from such termination, any Notes blocked in The Depository Trust Company ("DTC") will be released. Holders are advised to check with any bank, securities broker or other intermediary through which they hold Notes as to when such intermediary would need to receive instructions from a beneficial owner in order for that holder to be able to participate, or withdraw their instruction to participate, in the Offers before the deadlines specified herein and in the Offer to Purchase. The deadlines set by any such intermediary and DTC for the submission and withdrawal of tender instructions will also be earlier than the relevant deadlines specified herein and in the Offer to Purchase.

After the Price Determination Date, the Offerors may elect to redeem all or a portion of Bristol Myers Squibb’s 4.000% Notes due 2023 or 2.900% Notes due 2024 or Celgene’s 4.000% Notes due 2023 that are not tendered and accepted in the Offers in accordance with the terms of the optional redemption provisions in the indentures governing such Notes.

The Offerors have retained Deutsche Bank Securities Inc. and Morgan Stanley & Co. LLC as dealer managers for the Offers. Questions regarding terms and conditions of the Offers should be directed to Deutsche Bank Securities Inc. at (866) 627-0391 (toll-free) or (212) 250-2955 (collect) or Morgan Stanley & Co. LLC at (800) 624-1808 (toll-free) or (212) 761-1057 (collect). Global Bondholder Services Corporation will act as the tender agent and the information agent for the Offers (the "Tender and Information Agent").

The full details of the Offers, including instructions on how to tender Notes, are included in the Offer to Purchase. Holders are strongly encouraged to read carefully the Offer to Purchase, including documents incorporated by reference therein, because they will contain important information. The Offer to Purchase is available on Global Bondholder Services Corporation’s website at View Source or obtained from Global Bondholder Services Corporation at (866) 470-3800 (toll free) or (212) 430-3774 (collect). You may also contact your broker, dealer, commercial bank, trust company or other nominee for assistance concerning the Offers.

None of the Offerors or their affiliates, their respective boards of directors, the dealer managers, the Tender and Information Agent or the trustee with respect to the Notes is making any recommendation as to whether Holders should tender any Notes in response to the Offers, and neither the Offerors nor any such other person has authorized any person to make any such recommendation. Holders must make their own decision as to whether to tender any of their Notes, and, if so, the principal amount of Notes to tender.

This announcement is for informational purposes only. This announcement is not an offer to sell or purchase, a solicitation of an offer to sell or purchase, or the solicitation of tenders with respect to any of Notes described herein. The Offers are being made solely pursuant to the Offer to Purchase. The Offers are not being made to Holders of Notes in any jurisdiction in which the making or acceptance thereof would not be in compliance with the securities, blue sky or other laws of such jurisdiction. In any jurisdiction in which the securities laws or blue sky laws require the Offers to be made by a licensed broker or dealer, the Offers will be deemed to be made on behalf of the Offerors by the dealer managers or one or more registered brokers or dealers that are licensed under the laws of such jurisdiction.

This communication is not being made by, and has not been approved by, an authorized person for the purposes of Section 21 of the Financial Services and Markets Act 2000, as amended (the "FSMA)". Accordingly, this communication is not being distributed to, and must not be passed on to, persons within the United Kingdom save in circumstances where section 21(1) of the FSMA does not apply.

In particular, this communication is only addressed to and directed at: (A) in any Member State of the European Economic Area that has implemented the Prospectus Directive, qualified investors in that Member State within the meaning of the Prospectus Directive and (B) (i) persons that are outside the United Kingdom or (ii) persons in the United Kingdom falling within the definition of investment professionals (as defined in Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "Financial Promotion Order")) or within Article 43 of the Financial Promotion Order, or to other persons to whom it may otherwise lawfully be communicated under the Financial Promotion Order.

On February 4, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported virtual posters on its three skin cancer gene expression profile tests at the 19th Annual South Beach Symposium, taking place from Feb. 4 – 7, 2021 (Press release, Castle Biosciences, FEB 4, 2021, View Source [SID1234574633]).

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DecisionDx-Melanoma:

DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node (SLN) positivity, independent of traditional staging factors.

Castle Biosciences is highlighting data on DecisionDx-Melanoma with two posters. The first highlights new data and is entitled, "31-Gene expression profiling improves risk stratification in patients with T1 cutaneous melanoma."

Study methods and findings:

Nearly 70% of melanomas are diagnosed with tumor thickness that is less than or equal to 1.0 mm (T1 tumors), and recurrence-free survival (RFS) is generally good among these patients. However, up to 15% of patients with T1 tumors may experience a recurrence. Moreover, due to the large number of patients with T1 tumors, 27-30% of melanoma-related deaths occur in patients originally diagnosed with a T1 tumor, suggesting better identification of T1 patients at high risk of recurrence or metastasis is needed.
DecisionDx-Melanoma is designed to classify a patient’s recurrence risk as low (Class 1: Class 1A lowest) or high (Class 2: Class 2B highest) and has been validated in multiple prospective and retrospective studies.
Univariate analysis of the study data shows DecisionDx-Melanoma to be a stronger predictor of RFS than SLN status.
Multivariable analysis shows DecisionDx-Melanoma to be a strong, independent predictor of RFS.
With Class 2B RFS status similar to SLN positive status, Class 2B patients warrant follow-up strategies similar to SLN positive patients.
The second DecisionDx-Melanoma poster is entitled, "The clinical and financial impact of the 31-gene expression profile testing on sentinel lymph node biopsy patients selection in patients with T1b cutaneous melanoma."

Study methods and findings:

DecisionDx-Melanoma identifies patients with T1 tumors who have less than a 5% risk of SLN positivity and who have good survival outcomes. These outcomes suggest that such patients could forego the sentinel lymph node biopsy (SLNB) surgical procedure.
The authors analyzed all clinical DecisionDx-Melanoma tests that were reported from Jan. 3, 2019 through Sept. 4, 2020. The data showed that 75% of eligible patients with T1b tumors had a Class 1A result and could potentially forego SLNB. The authors estimate that foregoing SLNB in these patients could reduce healthcare expenditures by up to $120 million in SLNB-related costs.
DecisionDx DiffDx-Melanoma:

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions.

The virtual poster is entitled, "Development, Validation, and Clinical Utility of the 35-Gene Expression Profile Test for Use as an Adjunctive Melanoma Diagnostic Tool."

Study methods and findings:

DecisionDx DiffDx-Melanoma has demonstrated accuracy metrics of: 99.1% sensitivity, 94.3% specificity, 93.6% positive predictive value and 99.2% negative predictive value; the test also provides a modest intermediate-risk zone of 3.6% and a technical success rate of 96.6%.
Dermatopathologists who used DecisionDx DiffDx-Melanoma to refine their diagnoses in lesions reported increased diagnostic confidence by 51%. Dermatologists used the test result to gauge prognosis, case difficulty, office visit frequency and re-excisions, which were influenced by DecisionDx DiffDx-Melanoma’s result in the appropriate manner in most responses.
The diagnosis of challenging melanocytic lesions and subsequent clinical management decisions were determined to be influenced by the test in agreement with its result, potentially alleviating uncertainty in difficult-to-diagnose lesions. Therefore, DecisionDx DiffDx-Melanoma could lead to a potential increase in accurate diagnoses and focused reduction of burdensome and unnecessary procedures for cases that receive a benign DecisionDx DiffDx-Melanoma result.
DecisionDx-SCC:

DecisionDx-SCC is Castle’s prognostic gene expression profile test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC) designed to use a patient’s tumor biology to predict individual risk of metastasis for patients with SCC and one or more risk factors.

The virtual poster is entitled, "Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series."

"National guidelines for high-risk SCC patients leave room for subjectivity in assessing which patients warrant additional management," said study author and assistant professor of clinical dermatology at the Indiana University School of Medicine, Ally-Khan Somani, M.D., Ph.D. "Meanwhile, the incidence of SCC is rising with time, which increases the need for physicians to assess metastatic risk objectively for these patients, so that we can provide care accordingly. We have found that DecisionDx-SCC, by predicting tumor aggressiveness based on its gene expression, may stratify risk when integrated with commonly used staging factors to better inform SCC management decisions."

Study methods and findings:

Two SCC cases were presented that highlight DecisionDx-SCC’s utility in stratifying risk in SCC.
The cases were very similar at diagnosis, both presenting with a history of immunosuppression along with identical staging (T2a per Brigham and Women’s Hospital staging; T1 per American Joint Committee on Cancer staging), but had divergent outcomes:
Case 1 did not recur, despite incomplete resection.
Case 2 developed local recurrence and regional metastasis, and died from SCC, despite clear surgical margins, radiation and chemotherapy treatments.
Subsequent DecisionDx-SCC test results yielded risk level assignments that correlated with the two patients’ outcomes:
Case 1 had a retrospective low-risk (Class 1) DecisionDx-SCC result.
Case 2 had a highest-risk (Class 2B) DecisionDx-SCC result.
The authors concluded that incorporating DecisionDx-SCC as a prognostic factor with traditional clinicopathological risk factors can improve stratification of high-risk SCC patients with at least one risk factor, thereby informing risk-appropriate management strategies.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included more than 3,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through September 30, 2020, DecisionDx-Melanoma has been ordered more than 64,560 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

About DecisionDx DiffDx-Melanoma

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. DecisionDx DiffDx-Melanoma classifies these lesions as: benign (gene expression profile suggestive of benign neoplasm); intermediate-risk (gene expression profile cannot exclude malignancy); or malignant (gene expression profile suggestive of melanoma). Interpreted in the context of other clinical, laboratory and histopathologic information, DecisionDx DiffDx-Melanoma is designed to add diagnostic clarity and confidence for dermatopathologists while helping dermatologists deliver more informed patient management plans.

More information about the test and disease can be found at www.CastleTestInfo.com.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1, 2A or 2B risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

On February 4, 2021 Taiho Oncology, Inc. reported that updated guidelines on the use of LONSURF (trifluridine and tipiracil) have been included in the latest National Comprehensive Cancer Network Drugs and Biologics Compendium (NCCN Compendium) for Colon Cancer (Version 2.2021 – January 21, 2021) and Rectal Cancer (Version 1.2021 – December 22, 2020) (Press release, Taiho, FEB 4, 2021, View Source [SID1234574650]). Specifically, the "Colon Cancer"a and "Rectal Cancer"b sections of the NCCN Compendium, now include a Category 2A recommendation for trifluridine and tipiracil as subsequent therapy, either single agent or in combination with bevacizumab (per NCCN, an FDA-approved biosimilar is an appropriate substitute for bevacizumab), as treatment options for patients who have progressed through all available regimens.1

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LONSURF is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.2

The updated NCCN Compendium and Clinical Practice Guidelines are available at www.nccn.org.

About Metastatic Colorectal Cancer
Colorectal cancer is the fourth most commonly diagnosed cancer in the U.S.3 In 2020, there were an estimated 147,950 new cases and 53,200 deaths in the U.S.3 Approximately 22 percent of U.S. patients with colorectal cancer are diagnosed at the distant or metastasized stage.3 Metastatic colorectal cancer (mCRC) is associated with poor prognosis with a five-year survival rate of approximately 14.3 percent.3

Over the last decade, clinical outcomes for patients with mCRC have improved considerably due to the advent of novel treatment agents, predictive biomarkers, and a more strategic approach to the delivery of systemic therapies. Currently, the median overall survival for patients with mCRC being treated both in Phase III trials and in large observational series or registries is 30 months – more than double that of 20 years ago.4,5,6

About LONSURF2
LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase (TP) inhibitor, tipiracil, which increases trifluridine exposure by inhibiting its metabolism by TP. Trifluridine is incorporated into DNA, resulting in DNA dysfunction and inhibition of cell proliferation.

Since 2015, Taiho Pharmaceutical and Servier have been in an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico, and Asia.

Indications and Use
LONSURF is indicated for the treatment of adult patients with:

metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy
metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.
IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression:

LONSURF caused severe and life–threatening myelosuppression (Grade 3–4) consisting of neutropenia (38%), anemia (18%), thrombocytopenia (5%), and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection. A total of 12% of LONSURF–treated patients received granulocyte–colony stimulating factors. Obtain complete blood counts prior to and on day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, absolute neutrophil count less than 500/mm3, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose as clinically indicated.

Embryo–Fetal Toxicity:

LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breast–fed infant or the effects on milk production. Because of the potential for serious adverse reactions in breast–fed infants, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age or over who received LONSURF had a higher incidence of the following compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4 thrombocytopenia (7% vs 4%).

Hepatic Impairment: Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin greater than 1.5 times ULN and any AST) hepatic impairment. Patients with severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST) were not studied. No adjustment to the starting dose of LONSURF is recommended for patients with mild hepatic impairment.

Renal Impairment: No adjustment to the starting dosage of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m2.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in Patients Treated With LONSURF (≥5%): The most common adverse drug reactions in LONSURF–treated patients vs placebo–treated patients with mCRC, respectively, were asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), infections (27% vs 16%), abdominal pain (21% vs 18%), pyrexia (19% vs 14%), stomatitis (8% vs 6%), dysgeusia (7% vs 2%), and alopecia (7% vs 1%). In metastatic gastric cancer or gastroesophageal junction (GEJ), the most common adverse drug reactions, respectively were, nausea (37% vs 32%), decreased appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs 16%) and diarrhea (23% vs 14%).

Pulmonary emboli occurred more frequently in LONSURF–treated patients compared to placebo: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

Laboratory Test Abnormalities in Patients Treated With LONSURF: The most common laboratory test abnormalities in LONSURF–treated patients vs placebo-treated patients with mCRC, respectively, were anemia (77% vs 33%), neutropenia (67% vs 1%), and thrombocytopenia (42% vs 8%). In metastatic gastric cancer or GEJ, the test abnormalities, respectively, were neutropenia (66% vs 4%), anemia (63% vs 38%), and thrombocytopenia (34% vs 9%).

On February 4, 2021 Elucida Oncology, a biotechnology company based on C Dots – ultra-small nanoparticles developed at Cornell that show promise in identifying and fighting cancer – reported that secured $44 million in financing, in addition to $28 million raised in 2018 (Press release, Elucida Oncology, FEB 4, 2021, View Source [SID1234575245]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

A rendering of the molecular structure of a Cornell dot, which is smaller than 10 nanometers.
C Dots, originally called Cornell dots, were created more than 15 years ago in the lab of Uli Wiesner, the Spencer T. Olin Professor of Engineering in the Department of Materials Science and Engineering. Wiesner has been working to put C Dots to use in the fight against cancer ever since.

As a result of their size, C Dots proved safe and effective for use in human beings as both an imaging and a diagnostic tool in early clinical studies. The new funding will help the company gain regulatory approval as a targeted cancer therapeutic, and to expand its management team and its laboratory capabilities.

"This vote of support from investors means a lot to me," Wiesner said. "Given C Dots’ broad applicability, I have been pushing efforts in health care-focused startups since 2005 to commercialize this technology. At the beginning it was a reagent company. Then we started a company focusing on diagnostics, and now we have a company emphasizing therapeutics."

This evolution shows the flexibility and the value of the C Dot platform, he said.

Elucida was founded in 2014 and co-founders include Wiesner, Kai Ma, Ph.D. ’15, and Dr. Michelle Bradbury, director of intraoperative imaging at Memorial Sloan Kettering Cancer Center and professor of radiology at Weill Cornell Medicine.

In the C Dots, each silica-based nanoparticle has an embedded fluorescent molecule in the interior for optical detection, as well as several organic ligands and functional groups on the surface. This makes the C Dot platform more flexible: Specific ligands prevent attack from the body’s defenses, while targeting groups cause the C Dot to specifically bind with tumor cells when they come into contact.

In this configuration, C Dots are currently being tested as a diagnostic tool in ongoing clinical trials at Memorial Sloan Kettering and Weill Cornell Medicine. When they are injected into a person with cancer, the glowing C Dots attach to cancer cells and can be seen by the surgeon with the use of a fluorescent camera.

In order to gain regulatory approval as a targeted cancer therapeutic, the company will need to complete ongoing toxicology studies and file an Investigational New Drug application with the Food and Drug Administration, according to Geno Germano, CEO and president of Elucida. The latest round of funding will support these moves.

"We have an excellent technology, an incredible team at Elucida, and a world-class board to help us navigate the highly complex landscape around cancer therapeutics," Wiesner said.

Elucida is planning to start clinical trials this summer; by the spring of 2022, the company expects to have the first data from those trials.

"If this trial validates our therapeutic approach the way we think and hope it will," Wiesner said, "our C Dot nanoparticle platform will give us a whole battery of disease-fighting products."

Chris Dawson is a writer for the College of Engineering.