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 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that it will release fourth-quarter and full-year 2020 financial results before the market opens on Thursday, February 18, 2021, and will follow with a conference call to discuss the results and business expectations at 9:00 a.m. Eastern Time (Press release, West Pharmaceutical Services, FEB 4, 2021, View Source [SID1234574615]). To participate on the call, please dial 877-930-8295 (U.S.) or 253-336-8738 (International). The conference ID is 4095168.

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A live broadcast of the conference call will be available at the Company’s website, www.westpharma.com, in the "Investors" section. Management will refer to a slide presentation during the call, which will be made available on the day of the call. To view the presentation, select "Presentations" in the "Investors" section of the Company’s website.

An online archive of the broadcast will be available at the site three hours after the live call and will be available through Thursday, February 25, 2021, by dialing 855-859-2056 (U.S.) or 404-537-3406 (International). The conference ID is 4095168.

On February 4, 2021 Quanterix Corporation (Nasdaq: QTRX), a company digitizing biomarker analysis to advance the science of precision health, reported the pricing of its previously announced underwritten public offering of 3,571,428 shares of its common stock at a public offering price of $70.00 per share (Press release, Quanterix, FEB 4, 2021, View Source [SID1234574614]). All of the shares in the offering will be sold by Quanterix. Gross proceeds from the sale of the shares, before deducting underwriting discounts and commissions and offering expenses, are expected to be approximately $235.0 million. Quanterix has also granted the underwriters a 30-day option to purchase up to an additional 535,714 shares of common stock on the same terms and conditions.

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The offering is expected to close on or about February 8, 2021, subject to customary closing conditions.

Goldman Sachs & Co. LLC, SVB Leerink LLC and Cowen and Company, LLC are acting as joint bookrunning managers for the offering. Canaccord Genuity LLC is acting as lead manager for the offering.

The public offering is being made pursuant to a shelf registration statement on Form S-3ASR (File No. 333-249925) previously filed with the Securities and Exchange Commission ("SEC") on November 6, 2020, which automatically became effective upon filing. A preliminary prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website located at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to this offering, when available, can be obtained from Goldman Sachs & Co. LLC, 200 West Street, New York, NY 10282, Attention: Prospectus Department, by telephone at (866) 471-2526 or by e-mail at [email protected], from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA, 02110, by telephone at (800) 808-7525, ext. 6105 or by e-mail at [email protected], or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, by telephone at (833) 297-2926 or by email at [email protected].

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy, nor will there be any sale of these securities in any state or other jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On February 4, 2021 Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, reported pharmacodynamic (PD) activity results from the healthy volunteer portion of its randomized, placebo-controlled, double-blind Phase 1 trial of the company’s clinical candidate, exoIL-12 (Press release, Codiak Biosciences, FEB 4, 2021, View Source [SID1234574613]). Analyses of skin punch biopsies bordering the subcutaneous injection site of exoIL-12 revealed local retention of immunologically detectable IL-12 at the injection site, and localized pharmacological activity as measured by levels of the T cell attractant chemokine, IP-10, in the skin. IL-12 was not detected in plasma at any dose of exoIL-12 tested and plasma IP-10 was only detectable at the highest, 12 µg dose. Results confirmed the desired localization and retention of IL-12 at the injection site for at least 24 hours, as well as prolonged IP-10 production for 8-15 days depending upon dose.

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exoIL-12 is the first engineered exosome therapeutic candidate to be evaluated in humans and one of two Codiak programs currently in clinical development. exoIL-12 was engineered using the company’s proprietary engEx Platform and designed to display functional IL-12 – a potent anti-tumor cytokine – on the exosome surface using the exosomal protein, PTGFRN, as a scaffold.

"We now have clinical evidence in healthy volunteers of local, IL-12-driven pharmacology without detectable systemic exposure to IL-12 or drug-related adverse events for exoIL-12," said Benny Sorensen, M.D., Ph.D., Senior Vice President and Head of Clinical Development, Codiak. "These results further support the target profile that we are hoping to achieve with this candidate and have enabled us to identify the optimal dose for the next phase of our clinical program in patients with active, early-stage CTCL. Moreover, this data further validates the capacity of our engEx Platform to engineer precise properties into our exosome-based therapeutic candidates that potentially expand their therapeutic index."

These results are consistent with Codiak’s preclinical testing and confirm exoIL-12’s target product profile of local drug retention at the injection site, prolonged local pharmacodynamic activity, and lack of systemic IL-12 exposure. Codiak plans to initiate the next portion of the Phase 1 clinical trial, evaluating the safety and efficacy of exoIL-12, in cutaneous T Cell lymphoma (CTCL) patients at the dose of 6 µg, which Codiak believes to be the optimal pharmacologically active dose based upon this healthy volunteer data and prior preclinical data with exolL-12.

"We are pleased with the data we have obtained with exoIL-12 in healthy human volunteers and look forward to the initiation of trials in CTCL patients," said Douglas E. Williams, Ph.D., President and Chief Executive Officer, Codiak. "It is heartening to see one of the founding principles of Codiak validated in the current trial, namely that engineered exosomes can offer the opportunity to tailor therapeutic payloads to provide an active biological response while at the same time limiting unwanted side effects."

Pharmacodynamic Data from Healthy Volunteers

A total of five cohorts each with five subjects were enrolled, randomized 3:2 active drug to placebo, and dosed in the first part of the Phase 1 study. Each cohort received a subcutaneously administered single ascending dose of exoIL-12: 0.3 µg, 1.0 µg, 3.0 µg, 6.0 µg or 12.0 µg, respectively.

Pharmacodynamic (PD) measurements including skin IL-12 levels post-injection and IL-12 receptor-mediated signaling assessed by induction of IP-10, were measured in skin punch biopsies at a 1.5 cm radius from the subcutaneous injection site. Samples were collected immediately prior to dosing (placebo or exoIL-12) and at 24 hours, Day 8 and Day 15 after administration. Results showed detectable IL-12 near the injection site as much as 24 hours post injection at the 6 µg dose. Samples collected at the 8-day and 15-day time points did not have detectable IL-12. In contrast, doses from 1.0 µg to 12µg (not 0.3 µg) showed significant induction of IP-10 production in the skin detectable for 8-15 days confirming robust and durable local pharmacology. At the highest 12 µg dose, IP-10 was also detectable in the plasma, but not at any of the lower doses. As previously described, no detectable IL-12 was present in plasma and no drug-related adverse events were observed across the entire dose range. These results confirm the prolonged, local activation of the IL-12 signaling cascade and give us confidence that 6 µg is the optimal dose to move forward in the next phase of clinical testing in CTCL patients.

During the planned part two of the Phase 1 trial, repeat doses of exoIL-12 at 6 µg will be administered into the lesions of stage IA-IIB CTCL patients. Patients will be monitored for safety, pharmacokinetic, and PD effects through analysis of blood and tumor biopsies, and for local and systemic anti-tumor efficacy using validated CTCL assessment criteria, including CAILS and mSWAT scores. The study is being conducted in the United Kingdom. Given COVID-19-related restrictions involving new study initiation, Codiak is working closely with study sites to open enrollment and commence dosing of patients when allowable and appropriate. Safety, biomarker and preliminary anti-tumor efficacy results are anticipated by the end of 2021.

In prior clinical trials conducted by others of recombinant IL-12 (rIL-12), CTCL patients have shown single-agent treatment responses (56-74% overall response rate and up to 22% complete responses1). However, the utility of rIL-12 has been greatly limited due to serious adverse events caused by systemic exposure. To overcome these limitations, exoIL-12 was designed to facilitate dose control of IL-12 and limit systemic exposure and associated toxicity by localizing IL-12 in the tumor microenvironment (TME) in order to potentially expand the therapeutic index.

There is currently no standard of care treatment for early-stage CTCL. Physicians often employ a variety of non-specific interventions, including repetitive radiation therapy, photo therapy, high-potency steroids and local chemotherapy to inhibit tumor growth and halt disease progression. There is a need for treatments that can induce local as well as systemic anti-tumor activity.

About exoIL-12

exoIL-12 is Codiak’s exosome therapeutic candidate engineered to display fully active IL-12 on the surface of the exosome, using the exosomal protein, PTGFRN, as a scaffold, and designed to facilitate potent local pharmacology at the injection site with precisely quantified doses. By limiting systemic exposure of IL-12 and associated toxicity, Codiak hopes to enhance the therapeutic index with exoIL-12, delivering a more robust tumor response, dose control and an improved safety profile.

Codiak intends to focus development of exoIL-12 on tumors that have, in previous clinical testing, shown clinical responses to rIL-12 used as a monotherapy. This list includes CTCL, melanoma, Merkel cell carcinoma, Kaposi sarcoma, glioblastoma multiforme, triple negative breast cancer, among others.

On February 4, 2021 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported financial results for the fourth quarter and full year of 2020 (Press release, Alexion, FEB 4, 2021, View Source [SID1234574612]). Total revenues for the full year of 2020 were $6,069.9 million, a 22 percent increase compared to the same period in 2019. The negative impact of foreign currency on total revenues year-over-year was 1 percent, or $52.0 million, inclusive of hedging activities. On a GAAP basis, diluted EPS for the full year of 2020 was $2.72, compared to $10.70 in the prior year. Full year 2020 includes impairment charges of $2,053.3 million primarily relating to the KANUMA intangible asset and a related deferred tax benefit of $377.3 million. Full year 2019 includes one-time tax benefits of $382.2 million related to intra-entity asset transfers of intellectual property. Non-GAAP diluted EPS for the full year of 2020 was $12.51, a 19 percent increase versus the prior year.

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Total revenues in the fourth quarter were $1,591.8 million, a 15 percent increase compared to the same period in 2019. The positive impact of foreign currency on total revenues year-over-year was less than 1 percent, or $0.1 million, inclusive of hedging activities. On a GAAP basis, diluted EPS in the quarter was $2.42, compared to $4.00 in the prior year, inclusive of one-time tax benefits of $382.2 million related to intra-entity asset transfers of intellectual property in the fourth quarter of 2019. Non-GAAP diluted EPS for the fourth quarter of 2020 was $2.96, a 9 percent increase versus the fourth quarter of 2019.

"In 2020, we delivered on our LEAD-EXPAND-DIVERSIFY strategy – progressing our commercial portfolio with multiple global regulatory approvals, and further building our pipeline, which now spans more than 20 development programs. I am so proud of our team’s remarkable execution and perseverance amidst the uncertainties of COVID-19," said Ludwig Hantson, Ph.D., Chief Executive Officer of Alexion. "We enter 2021 with significant momentum, a strong foundation and a promising future. I am confident we are well positioned to build on our success and further advance our mission of delivering life-changing medicines to people with rare diseases and devastating conditions in the coming months and once we become part of AstraZeneca."

Full Year 2020 Financial Highlights

Net product sales were $6,069.1 million, compared to $4,990.0 million in 2019.
SOLIRIS net product sales were $4,064.2 million, compared to $3,946.4 million in 2019, representing a 3 percent increase.
ULTOMIRIS net product sales were $1,076.7 million, compared to $338.9 million in 2019, representing a 218 percent increase.
STRENSIQ net product sales were $731.8 million, compared to $592.5 million in 2019, representing a 24 percent increase.
KANUMA net product sales were $117.9 million, compared to $112.2 million in 2019, representing a 5 percent increase.
ANDEXXA/ONDEXXYA net product sales were $78.5 million.
GAAP cost of sales was $553.5 million, compared to $394.5 million in 2019. Non-GAAP cost of sales was $518.2 million, compared to $380.3 million in 2019.
GAAP R&D expense was $1,002.9 million, compared to $886.0 million in 2019. Non-GAAP R&D expense was $929.4 million, compared to $720.9 million in 2019.
GAAP SG&A expense was $1,399.9 million, compared to $1,261.1 million in 2019. Non-GAAP SG&A expense was $1,198.6 million, compared to $1,099.9 million in 2019.
GAAP impairment of intangible assets was $2,053.3 million primarily related to an impairment charge recorded during the second quarter 2020 related to the KANUMA intangible asset.
GAAP income tax benefit was $34.4 million, compared to $225.5 million in 2019. GAAP income tax benefit for 2020 includes a deferred tax benefit of $377.3 million associated with the impairment charge related to the KANUMA intangible asset. GAAP income tax benefit for 2019 includes one-time tax benefits of $382.2 million related to intra-entity asset transfers of intellectual property in 2019. Non-GAAP income tax expense was $512.8 million, compared to $359.4 million in 2019.
GAAP diluted EPS was $2.72, compared to $10.70 in 2019. GAAP diluted EPS for 2020 includes impairment charges of $2,053.3 million primarily relating to the KANUMA intangible asset, offset by a deferred tax benefit of $377.3 million associated with the KANUMA impairment charge. GAAP diluted EPS for 2019 includes one-time tax benefits of $382.2 million related to intra-entity asset transfers of intellectual property in 2019. Non-GAAP diluted EPS was $12.51, compared to $10.53 in 2019.
Fourth Quarter 2020 Financial Highlights

Net product sales were $1,591.7 million in the fourth quarter of 2020, compared to $1,384.2 million in the fourth quarter of 2019.
SOLIRIS net product sales were $1,023.5 million, compared to $1,013.1 million in the fourth quarter of 2019, representing a 1 percent increase.
ULTOMIRIS net product sales were $313.5 million, compared to $170.2 million in the fourth quarter of 2019, representing an 84 percent increase.
STRENSIQ net product sales were $185.9 million, compared to $166.8 million in the fourth quarter of 2019, representing an 11 percent increase.
KANUMA net product sales were $29.2 million, compared to $34.1 million in the fourth quarter of 2019, representing a 14 percent decrease.
ANDEXXA/ONDEXXYA net product sales were $39.6 million in the fourth quarter of 2020.
GAAP cost of sales was $152.2 million, compared to $114.3 million in the fourth quarter of 2019. Non-GAAP cost of sales was $138.0 million, compared to $110.8 million in the fourth quarter of 2019.
GAAP R&D expense was $295.0 million, compared to $269.6 million in the fourth quarter of 2019. Non-GAAP R&D expense was $269.8 million, compared to $226.7 million in the fourth quarter of 2019.
GAAP SG&A expense was $444.4 million, compared to $381.0 million in the fourth quarter of 2019. Non-GAAP SG&A expense was $384.6 million, compared to $340.0 million in the fourth quarter of 2019.
GAAP income tax expense was $54.8 million, compared to income tax benefit of $287.0 million in the fourth quarter of 2019, inclusive of one-time tax benefits related to intra-entity asset transfers of intellectual property in the fourth quarter of 2019. Non-GAAP income tax expense was $111.0 million, compared to $85.8 million in the fourth quarter of 2019.
GAAP diluted EPS was $2.42, compared to $4.00 in the fourth quarter of 2019, inclusive of one-time tax benefits related to intra-entity asset transfers of intellectual property in the fourth quarter of 2019. Non-GAAP diluted EPS was $2.96, compared to $2.71 in the fourth quarter of 2019.
COVID-19

We continue to take steps to proactively respond to the evolving COVID-19 pandemic and to plan for related uncertainties. We remain focused on continuing to serve patients, protecting the health and safety of our employees and the communities in which we live and work, and supporting patients in clinical trials. We are also focused on minimizing potential interactions that could contribute to the spread of the virus and put additional strain on healthcare systems through the use of innovative virtual means where possible.

Clinical Trials: We have implemented a pandemic response business continuity plan designed to protect patients and site staff safety while continuing our clinical trials with limited interruption to the extent we are able. The COVID-19 impact has varied by study and program, but there has been little timing impact on fully-enrolled trials. By the third quarter of 2020, we had successfully re-initiated the majority of studies that had been temporarily paused earlier in the year. However, increasing COVID-19 cases have had further effects on the timing of healthy volunteer studies in particular. In addition, there has been, and may continue to be, an impact to the timing of trials that are enrolling patients and activating sites, or have not yet started to do so, based on local dynamics where these studies are being conducted.
Business Impact: We continue to take proactive measures designed to mitigate the risk of potential interruptions in supply and/or access to patients’ customary site-of-care locations. Treatment compliance rates across all our medicines have remained strong. We have also seen the predicted slowing of new patient initiations and delays in treatment starts, and we are continuing to closely monitor this environment as the pandemic continues.
Research and Development

PHASE 3/4

SOLIRIS – Guillain-Barre Syndrome (GBS): SOLIRIS in GBS has been granted SAKIGAKE designation by Japan’s Ministry of Health, Labour and Welfare (MHLW). Alexion plans to initiate a Phase 3 study of SOLIRIS in GBS in Japan in the first half of 2021.
ULTOMIRIS – 100 mg/mL: In November 2020, the ULTOMIRIS 100 mg/mL formulation for PNH and aHUS was approved in the EU. An application for approval is under review in Japan. This higher concentration formulation is designed to reduce infusion time by more than 60 percent to approximately 45 minutes.
ULTOMIRIS – Subcutaneous: The Phase 3 study of weekly subcutaneous (SC) ULTOMIRIS demonstrated PK-based non-inferiority versus intravenous ULTOMIRIS. Pending collection of 12-month safety and drug-device combination data, Alexion plans to file for approval in the U.S. and EU for the ULTOMIRIS SC formulation and device combination in PNH and aHUS in the third quarter of 2021.
ULTOMIRIS – gMG: In November 2020, Alexion completed enrollment in the Phase 3 study of ULTOMIRIS in adults with gMG. Study results are expected in the second half of 2021.
ULTOMIRIS – NMOSD: A Phase 3 study of ULTOMIRIS in NMOSD is underway.
ULTOMIRIS – Amyotrophic Lateral Sclerosis (ALS): As completion of full enrollment nears, screening of new patients has closed for the Phase 3 study of ULTOMIRIS in ALS.
ULTOMIRIS – Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA): Dosing is underway in Phase 3 studies of ULTOMIRIS in adults and children with HSCT-TMA.
ULTOMIRIS – Complement Mediated Thrombotic Microangiopathy (CM-TMA): In January 2021, Alexion submitted an Investigational New Drug (IND) application for ULTOMIRIS in CM-TMA and plans to initiate a Phase 3 study in the first half of 2021.
ULTOMIRIS – Severe COVID-19: In January 2021, Alexion paused further enrollment in a Phase 3 trial of ULTOMIRIS in adults hospitalized with severe COVID-19 requiring mechanical ventilation, due to lack of efficacy, pending further analysis of the data. This decision was made based on the recommendation of an independent data monitoring committee, following their review of data from a pre-specified interim analysis. Alexion continues to provide ULTOMIRIS for the ongoing TACTIC-R platform study led by Cambridge University Hospitals NHS Foundation Trust, which is evaluating the potential of earlier immune modulatory treatment (hospitalized patients not requiring mechanical ventilation) in preventing progression of the virus.
ULTOMIRIS – Dermatomyositis (DM): Alexion plans to initiate a Phase 2/3 study of ULTOMIRIS in DM in the second half of 2021, pending regulatory feedback.
ALXN1840 – Wilson Disease: Enrollment is complete in a Phase 3 study of ALXN1840 in Wilson disease. Study results are expected in the first half of 2021.
CAEL-101 – Caelum Biosciences: Alexion and Caelum Biosciences are conducting the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101, a first-in-class amyloid fibril targeted therapy, in combination with standard-of-care therapy in AL amyloidosis. Dosing is underway in two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease and one in patients with Mayo stage IIIb disease.
ALXN2060 (AG10): Alexion holds an exclusive license to develop and commercialize ALXN2060 (AG10) in Japan. Eidos is currently evaluating AG10 in two Phase 3 studies in the U.S. and Europe – one for ATTR cardiomyopathy (ATTR-CM) and one for ATTR polyneuropathy (ATTR-PN). In October 2020, Alexion initiated a Phase 3 bridging study of ALXN2060 for patients with ATTR-CM in Japan and dosing is underway.
ALXN2040 (Danicopan) – PNH with Extravascular Hemolysis (EVH): In December 2020, Alexion initiated a Phase 3 study of ALXN2040 as an add-on therapy for PNH patients with EVH and dosing is underway.
ANDEXXA – Acute Intracranial Hemorrhage (ICH): The Phase 4 ANNEXA-I study – designed to provide clinical data supporting full approval – is underway to assess ANDEXXA compared to usual standard of care in patients presenting with acute intracranial hemorrhage while taking an oral Factor Xa inhibitor. In December 2020, Alexion submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA to enable the addition of edoxaban and enoxaparin to the U.S. label. Alexion plans to file for regulatory approval of ANDEXXA in Japan in the first quarter of 2021.
PHASE 1/2

ULTOMIRIS – Renal Diseases: In November 2020, Alexion initiated a proof-of-concept study of ULTOMIRIS in patients with IgA nephropathy and lupus nephritis.
ALXN1830: Due to COVID-19, Alexion discontinued the Phase 2 study of ALXN1830, administered intravenously, in warm autoimmune hemolytic anemia (WAIHA) and the Phase 1 study of a subcutaneous formulation of ALXN1830 in healthy volunteers. In January 2021, a Clinical Trial Application (CTA) for a new Phase 1 study of subcutaneous ALXN1830 was approved in New Zealand; study initiation is planned for the first quarter of 2021. Following successful completion of the Phase 1 study, Alexion plans to initiate Phase 2 studies of subcutaneous ALXN1830 in gMG and WAIHA in 2021, pending regulatory feedback.
ALXN2040 – Geographic Atrophy (GA): Alexion plans to initiate a Phase 2 study of ALXN2040 in GA in the second half of 2021.
ALXN2040 – COVID-19: Alexion has agreed to provide ALXN2040 to the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, for the ACTIV-5 Big Effect Trial in adults hospitalized with COVID-19. This Phase 2 platform trial is comparing different investigational therapies to a common control arm with the intent of identifying promising treatments to enter a more definitive study.
ALXN2050 – PNH: Alexion has paused additional enrollment in the Phase 2 study of ALXN2050 monotherapy in PNH patients, pending the receipt of further Phase 1 data (expected in the second quarter of 2021) that will allow for dose escalation in the Phase 2 study.
ALXN2050 – Renal Diseases: Alexion plans to initiate a proof-of-concept study of ALXN2050 in patients with various renal diseases in 2021, pending regulatory feedback.
ALXN1720: The Phase 1 healthy volunteer study of ALXN1720, a novel anti-C5 albumin-binding bi-specific mini-body that is designed to bind and prevent activation of human C5, has been paused for a second time due to COVID-19. Additional cohorts have been added to the study to explore higher doses and enable the initiation of a Phase 3 study in gMG, pending successful completion of the Phase 1 study as has been agreed with the FDA. Data from the Phase 1 study are expected in the second half of 2021. Alexion also plans to initiate a study of ALXN1720 in DM.
ANDEXXA – Urgent Surgery: ANDEXXA is currently being evaluated in a single-arm, open-label Phase 2 study in patients taking apixaban, rivaroxaban, edoxaban, or enoxaparin who require urgent surgery. The results of this study will inform the design of a randomized controlled Phase 3 clinical trial to expand the label in this population.
ALXN2075 (cerdulatinib): Acquired as part of the Portola acquisition, ALXN2075 is a dual spleen tyrosine kinase and janus kinase (SYK/JAK) inhibitor being evaluated in a Phase 1/2a study in patients with relapsed/refractory chronic lymphocytic leukemia or B-cell or T-cell non-Hodgkin lymphoma. Data are expected in the first half of 2021.
ALXN1820: In January 2021, Alexion initiated a Phase 1 study of ALXN1820, its bi-specific anti-properdin mini-body, in healthy volunteers.
ALXN1850 – Hypophosphatasia (HPP): In November 2020, Alexion submitted an IND application to the FDA for ALXN1850, its next generation asfotase alfa asset. Initiation of a Phase 1 study in adults with HPP is planned for the second quarter of 2021.
Conference Call/Earnings Materials:

Given the recently announced agreement for Alexion to be acquired by AstraZeneca, Alexion will not be hosting a conference call. Earnings materials are available publicly on the Investor Relations page of our website at View Source Questions may be directed to the Investor Relations team via e-mail at [email protected] or the contact information below.