On March 10, 2021 Avid Bioservices, Inc. (NASDAQ:CDMO) (NASDAQ:CDMOP) (the "company"), a dedicated biologics contract development and manufacturing organization (CDMO) working to improve patient lives by providing high quality development and manufacturing services to biotechnology and pharmaceutical companies, reported that its wholly-owned subsidiary, Avid SPV, LLC (the "Issuer"), has priced its sale of $125 million aggregate principal amount of exchangeable senior notes due 2026 (the "notes") in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Avid Bioservices, MAR 10, 2021, View Source [SID1234576385]). The issuance and sale of the notes are scheduled to settle on March 12, 2021, subject to customary closing conditions. The Issuer also granted the initial purchasers of the notes a 13-day option to purchase up to an additional $18.75 million aggregate principal amount of the notes.

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The notes will be senior, unsecured obligations of the Issuer, will be fully and unconditionally guaranteed by the company on a senior, unsecured basis, and will accrue interest at a rate of 1.250% per annum payable semi-annually in arrears on March 15 and September 15 of each year, beginning on September 15, 2021. The notes will mature on March 15, 2026, unless earlier repurchased, redeemed or exchanged. Before September 15, 2025, noteholders will have the right to exchange their notes only upon the occurrence of certain events. From and after September 15, 2025, noteholders may exchange their notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date of the notes. The notes will be settled in cash, shares of the company’s common stock or a combination of cash and shares of the company’s common stock, at the Issuer’s election.

The initial exchange rate is 47.1403 shares of the company’s common stock per $1,000 principal amount of notes (which represents an initial exchange price of approximately $21.21 per share of the company’s common stock). The initial exchange price represents a premium of approximately 32.5% over the last reported sale price of $16.01 per share of the company’s common stock on March 9, 2021. The exchange rate and exchange price of the notes will be subject to adjustment upon the occurrence of certain events.

The notes will be redeemable, in whole or in part, for cash at the Issuer’s option at any time, and from time to time, on or after March 20, 2024 if the last reported sale price of the company’s common stock has been at least 130% of the exchange price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which the Issuer provides notice of redemption at a redemption price equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date.

If a "fundamental change" (as defined in the indenture for the notes) occurs, then noteholders may require the Issuer to repurchase their notes for cash. The repurchase price will be equal to the principal amount of the notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the applicable repurchase date.

The net proceeds from the offering are estimated to be approximately $120.6 million (or approximately $138.7 million if the initial purchasers fully exercise their option to purchase additional notes), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses. The Issuer expects to make an intercompany loan to the company of all of the net proceeds from this offering. The company intends to use approximately $11.2 million of such loan to pay the cost of the capped call transactions described below, and to use up to approximately $41.3 million of such loan to redeem all of the company’s outstanding 10.50% Series E Convertible Preferred Stock (assuming such redemption occurs on April 10, 2021, all such shares remain outstanding through such date and none of such shares are converted into the company’s common stock prior to such redemption). The company intends to use the remaining net proceeds for working capital and other general corporate purposes. If the initial purchasers exercise their option to purchase additional notes, the Issuer expects to make an intercompany loan to the company of all of the net proceeds from the sale of additional notes, which the company intends to use to pay the cost of additional capped call transactions and for working capital and other general corporate purposes. The company may also use a portion of such loans for the acquisition of, or investment in, technologies, solutions or businesses that complement the company’s business, although it has no commitments to enter into any such acquisitions or investments at this time.

In connection with the pricing of the notes, the company entered into privately negotiated capped call transactions with the initial purchasers or their affiliates (the "option counterparties"). The capped call transactions cover, subject to customary adjustments, the number of shares of the company’s common stock that initially underlie the notes. The capped call transactions are expected to reduce or offset the potential dilution of the company’s common stock as a result of any exchange of the notes and/or offset any potential cash payments the Issuer is required to make in excess of the principal amount of exchanged notes, as the case may be, with such reduction and/or offset subject to a cap. If the initial purchasers exercise their option to purchase additional notes, the company expects to enter into additional capped call transactions with the option counterparties. The cap price of the capped call transactions will initially be approximately $28.02 per share of the company’s common stock, which represents a premium of approximately 75.0% over the last reported sale price of the company’s common stock of $16.01 per share on March 9, 2021, and is subject to certain adjustments under the terms of the capped call transactions.

In connection with establishing their initial hedges of the capped call transactions, the option counterparties and/or their respective affiliates may purchase shares of the company’s common stock and/or enter into various derivative transactions with respect to the company’s common stock concurrently with, or shortly after, the pricing of the notes, including with certain investors in the notes. This activity could increase (or reduce the size of any decrease in) the market price of the company’s common stock or the notes at that time.

In addition, the option counterparties and/or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to the company’s common stock and/or purchasing or selling the company’s common stock or other securities in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so on each exercise date for the capped call transactions, which are expected to occur during the 40 trading day period beginning on the 41st scheduled trading day prior to the maturity date of the notes). This activity could also cause or avoid an increase or decrease in the market price of the company’s common stock or the notes, which could affect the ability of noteholders to exchange the notes, and, to the extent the activity occurs during any observation period related to an exchange of notes, it could affect the number of shares of the company’s common stock and value of the consideration that holders of the notes will receive upon exchange of the notes.

Neither the notes, nor any shares of the company’s common stock potentially issuable upon exchange of the notes, have been, nor will be, registered under the Securities Act or any state securities laws and, unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any securities, nor shall it constitute an offer, solicitation or sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction. The notes will be offered to qualified institutional buyers pursuant to Rule 144A under the Securities Act.

On March 10, 2021 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for LNS8801 for the treatment of patients with metastatic uveal melanoma (MUM) (Press release, Linnaeus Therapeutics, MAR 10, 2021, View Source [SID1234576383]).

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The FDA’s Office of Orphan Drug Products grants orphan drug status to support drug candidates in development for underserved patient populations or rare disorders that affect fewer than 200,000 people in the United States. Orphan drug designation provides certain benefits, including market exclusivity upon FDA approval, exemption of FDA application fees, and tax credits for qualified clinical trials.

"We are extremely pleased to have received orphan drug designation for MUM from the FDA. This is an important milestone that has emerged from the very promising data we have seen in patients with MUM during dose escalation," commented Patrick Mooney, MD, CEO of Linnaeus. "We look forward to further exploring the preliminary results with LNS8801 alone and also in combination with pembrolizumab when we open additional cohorts soon."

Having completed dose escalation, Linnaeus is currently testing LNS8801 in its phase 1/2 adaptive-design clinical trial as a monotherapy and in combination with KEYTRUDA (pembrolizumab) in patients who had previous clinical benefit from immune checkpoint inhibitors and then subsequently progressed. This marks the first time any company has dosed a patient in a clinical trial specifically targeting the G protein-coupled estrogen receptor (GPER) in combination with pembrolizumab. Linnaeus intends to open a LNS8801 monotherapy cohort in patients with MUM and also a combination therapy cohort testing LNS8801 and pembrolizumab in patients with MUM in the near term as well as other targeted indications.

About LNS8801
LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing phase 1/2 study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancer. Data from the phase 1/2 study are anticipated to be presented in a peer-reviewed setting in 2021.

On March 10, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI), a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic which addresses a fundamental biologic mechanism of immune suppression in cancer, reported that management will present at the Oppenheimer & Co. Annual Healthcare Conference which is being held Tuesday, March 16th – Thursday, March 18th, 2021 (Press release, Infinity Pharmaceuticals, MAR 10, 2021, View Source [SID1234576382]). Presentation details are as follows:

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Oppenheimer & Co. Annual Healthcare Conference Company Presentation:

Date:

Wednesday, March 17

Time:

1:10 pm Eastern Time

Webcast:

View Source

The webcast of the presentation can be accessed in the Investors/Media section of Infinity’s website at www.infi.com and will be available on Infinity’s website for 30 days following the event.

On March 10, 2021 bluebird bio, Inc. (Nasdaq: BLUE) reported that based on the analyses completed to date, it is very unlikely the Suspected Unexpected Serious Adverse Reaction (SUSAR) of acute myeloid leukemia (AML) reported in its Phase 1/2 (HGB-206) study of LentiGlobin gene therapy for sickle cell disease (SCD) (bb1111) was related to the BB305 lentiviral vector (LVV) (Press release, bluebird bio, MAR 10, 2021, View Source [SID1234576381]).

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"In addition to our earlier findings of several well-known genetic mutations and gross chromosomal abnormalities commonly observed in AML in this patient, our latest analyses identified the integration site for the vector within a gene called VAMP4. VAMP4 has no known association with the development of AML nor with processes such as cellular proliferation or genome stability. Moreover, we see no significant gene misregulation attributable to the insertion event," said Philip Gregory, chief scientific officer, bluebird bio. "In totality, the data from our assessments provide important evidence demonstrating that it is very unlikely our BB305 lentiviral vector played a role in this case and we have shared with the FDA that we believe these results support lifting the clinical holds on our β-thalassemia and sickle cell disease programs."

As reported by bluebird bio on February 25, 2021, laboratory analyses showed that this patient had significant chromosomal abnormalities and mutations in genes typically associated with the development of AML. Specifically, mutations in the RUNX1 and PTPN11 genes have been detected in the leukemic cells of this patient. Preliminary findings suggested that the BB305 LVV vector was present in the AML blast cells, but there was not sufficient information to determine causality.

Since then, and with the advice of several independent leading academic experts in lentiviral vector gene therapy, bluebird bio has performed additional scientific assessments to determine where in the genome the LVV insertion occurred, and if this integration was responsible for any change in gene regulation or gene expression nearby.

Multiple independent analyses have confirmed that vector insertion in the AML cells from this patient took place in the VAMP4 gene, or vesicle-associated membrane protein 4. VAMP4 itself has no known role in the development of AML or with any cellular process related to cancer.

bluebird bio also assessed if there was any disruption to normal gene regulation or gene expression in and around the site of vector insertion. Based on completed analyses, the insertion into the VAMP4 gene has had no impact on gene expression or gene regulation nor caused any disruption of nearby genes.

Based on the available results to date, bluebird bio believes that the case of AML is very unlikely related to the BB305 LVV. Given this, the company has initiated engagement with regulators to begin the process of resuming clinical studies for sickle cell disease and β-thalassemia.

A second SUSAR of myelodysplastic syndrome (MDS) in a patient from Group C of HGB-206 was reported in early February and is currently being investigated to determine if the clinical findings meet the criteria to be classified as a case of MDS and, if so, if LentiGlobin for SCD had any role. The MDS diagnosis was based on prolonged anemia following LentiGlobin for SCD infusion coupled with the observation of trisomy 8 in a small percentage of the patient’s bone marrow cells. However, no blasts or dysplastic cells were seen in an examination of the patient’s bone marrow, and while trisomy 8 is associated with myeloid malignancies, this finding is not sufficient for a diagnosis of MDS in the absence of blasts or dysplastic cells.

Regulatory Status

The U.S. Food and Drug Administration (FDA) has placed a clinical hold on the HGB-206 and HGB-210 studies of LentiGlobin for SCD and the HGB-207 and HGB-212 studies of betibeglogene autotemcel for β-thalassemia. The company is in dialogue with the FDA in order to resume all clinical studies currently on clinical hold.

An Article 20 referral procedure was triggered by the European Commission (EC) and will be conducted by the European Medicines Agency (EMA). The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) will begin the process of reviewing the benefit/risk of ZYNTEGLO (betibeglogene autotemcel) for the treatment of transfusion-dependent β-thalassemia, during its March 8 – 11 session. The committee will determine whether any additional pharmacovigilance measures are necessary. The EMA has paused the renewal procedure for ZYNTEGLO’s conditional marketing authorization (CMA) while the PRAC review is ongoing.

No cases of hematologic malignancy have been reported in any patient who has received treatment with betibeglogene autotemcel for transfusion-dependent β-thalassemia, however because it is also manufactured using the same BB305 LVV used in LentiGlobin for SCD, the company decided to temporarily suspend marketing of ZYNTEGLO while the AML case is assessed.

Investor Conference Call Information

bluebird bio will hold a conference call to discuss this update on Wednesday, March 10 at 8:00 a.m. ET. Investors may listen to the call by dialing (844) 825-4408 from locations in the United States or +1 (315) 625-3227 from outside the United States. Please refer to conference ID number 4148389.

To access the live webcast of bluebird bio’s presentation, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 90 days following the event.

About HGB-206 and HGB-210

HGB-206 is a Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A, B and C. A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

HGB-210 is a Phase 3 single-arm open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for SCD in patients between two years and 50 years of age with sickle cell disease.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bio’s clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the Phase 1/2 HGB-206 study, and the Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the EMA in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: View Source or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About ZYNTEGLO (betibeglogene autotemcel)

Betibeglogene autotemcel (beti-cel) is a one-time gene therapy that adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the βA-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived adult Hb, at levels that may eliminate or significantly reduce the need for transfusions. In studies of beti-cel, transfusion independence (TI) is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

The European Commission granted conditional marketing authorization (CMA) for beti-cel, marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent β-thalassemia (TDT) who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity, tachycardia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

For details, please see the Summary of Product Characteristics (SmPC).

On April 28, 2020, the EMA renewed the CMA for beti-cel. The CMA for beti-cel is valid in the 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. In November 2020, bluebird bio submitted to the EMA an application for renewal of the CMA; this procedure is currently on hold. The CMA is valid while the renewal application review is ongoing and while it is on hold.

The U.S. Food and Drug Administration granted beti-cel Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT. Beti-cel is not approved in the U.S. Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies.

bluebird bio is conducting a long-term safety and efficacy follow-up study, LTF-303 for people who have participated in bluebird bio-sponsored clinical studies of ZYNTEGLO.

On March 10, 2021 Leidos (NYSE: LDOS), a FORTUNE 500 science and technology company, reported that it will participate in the Bank of America Global Industrials Conference 2021 webcast (Press release, Leidos, MAR 10, 2021, View Source [SID1234576380]).

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Jim Reagan, Chief Financial Officer, will participate in a question and answer "fireside chat" on Wednesday, March 17, 2021 at 3:00 p.m. ET.

A live audio webcast of the event will be available on the Leidos Investor Relations website at View Source A replay of the webcast will be available following the presentation at the same link listed above until September 14, 2021.