Repertoire Immune Medicines and Dana-Farber Cancer Institute Collaborate to Identify Novel Antigen Targets Within HPV+ Head and Neck Cancers

On February 11, 2021 Repertoire Immune Medicines, a clinical-stage biotech company creating a new category of immune therapies for cancer, autoimmunity and infectious disease, reported a research collaboration with Dana-Farber Cancer Institute to advance discovery and clinical development in human papillomavirus-positive (HPV+) oropharyngeal (head and neck) cancers (Press release, Repertoire, FEB 11, 2021, View Source [SID1234574951]). Through this collaboration, Dana-Farber and Repertoire aim to identify novel tumor antigen targets relevant to HPV+ head and neck tumors that will be used to inform the development of novel therapeutic candidates.

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As part of the collaboration, Dana-Farber will provide blood and tissue samples from patients with newly diagnosed, or with late-stage, recurrent HPV+ oropharyngeal cancer. Repertoire will use its DECODE platform to identify novel antigens and evaluate tumor antigen expression as well as profile the tumor microenvironment. The results of this research collaboration will inform Repertoire’s selection of tumor antigens for T cell therapy investigation that have the potential to be integrated into clinical trials.

Dana-Farber’s engagement is led by Glenn Hanna, M.D., Director, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber; Ravindra Uppaluri, M.D., Ph.D., Director of Head and Neck Surgical Oncology, Brigham and Women’s Hospital and Dana-Farber; and Ann Marie Egloff, Ph.D., Lead Investigator in the Department of Surgery, Brigham and Women’s Hospital and a Dana-Farber affiliate investigator.

"While many with human papillomavirus (HPV)-positive oropharyngeal cancer are cured, there remains an urgent need for new treatments among those with recurrent or incurable disease. We are hopeful that the application of Repertoire’s cutting-edge antigen decoding technology will enable the design of more effective medicines that utilize the immune system to combat cancer," said Hanna.

"We are delighted to be collaborating with the world-renowned Dana-Farber Cancer Institute as we work together to obtain novel insights into antigen expressions for patients with HPV-positive cancers," said Anthony Coyle, Ph.D., President, Research and Development, Repertoire. "We believe this collaboration has the potential to yield breakthrough science through our complementary capabilities to discover novel immune medicines."

This research engagement is the second collaboration between Dana-Farber and Repertoire. Dana-Farber is currently a site for an ongoing Phase I clinical trial of Repertoire’s PRIME IL-15, a novel, autologous, non-genetically modified multiclonal T cell product designed to release IL-15 in a local and sustained manner, limiting systemic exposure and thus improving tolerability. Sarah Nikiforow, M.D., Ph.D., Medical Oncology, Dana-Farber, is principal investigator on this study. More information is available on www.ClinicalTrials.gov, Study Identifier Number NCT03815682.

AVEO Oncology Announces Presentation of Key Subgroup and Quality of Life Analyses from the Phase 3 TIVO-3 Study of Tivozanib in Renal Cell Carcinoma

On February 11, 2021 AVEO Oncology (Nasdaq: AVEO) reported the presentation of two analyses of the Company’s pivotal TIVO-3 study, its Phase 3 trial comparing tivozanib, AVEO’s next-generation vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI) drug candidate, to sorafenib in third- and fourth-line renal cell carcinoma (RCC) (Press release, AVEO, FEB 11, 2021, View Source [SID1234574949]). The data are being presented in a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary (GU) Cancers Symposium being held virtually.

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"Data reported today continue to support tivozanib’s differentiation among TKIs and its potential to serve as a meaningful option for RCC patients who have relapsed or become refractory to multiple lines of therapy," said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center. "Of note, sequencing data suggest differential activity between tivozanib and axitinib, despite both being potent and selective VEGF TKIs. With no existing evidence-based standard of care for this historically difficult-to-treat population, tivozanib could potentially play a key role in the evolving relapsed or refractory RCC treatment landscape."

"These findings enhance our understanding of tivozanib in a clinically relevant patient population and add to the body of data from TIVO-3, which, as the first positive superiority study in patients who have relapsed or become refractory to two or more systemic therapies, could potentially serve as an important guide for treatment decisions in this setting," said Michael Bailey, president and chief executive officer of AVEO. "As we await the U.S. Food and Drug Administration’s decision on our New Drug Application submission for tivozanib as a treatment for relapsed or refractory RCC, we remain focused on commercial preparations to support a robust potential U.S. launch. We are committed to our mission of improving both outcomes and patient experience, and to ensuring that tivozanib becomes available to as many appropriate patients as possible."

ASCO GU Data

Q-TWiST Analysis. A poster titled, "Q-TWiST analysis of tivozanib versus sorafenib in patients with advanced renal cell carcinoma (RCC) in the TIVO-3 study" (abstract 298) highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess health-related quality of life. Findings showed that tivozanib significantly increased Q-TWiST relative to sorafenib in patients treated in the TIVO-3 study (15.04 months vs. 12.78 months; p=0.0493), and tivozanib nearly doubled Q-TWiST compared to sorafenib (10.30 months vs. 5.35 months.) These data suggest that tivozanib may convey tolerability advantages as measured by a patient-centered health-related patient quality of life. Q-TWiST analyses have previously been used to assess other TKIs for the treatment of RCC.
Prior Axitinib Therapy. A presentation titled, "Tivozanib in Patients with Advanced Renal Cell Carcinoma (aRCC) who have Progressed After Prior Treatment with Axitinib: Results from TIVO-3" (abstract 278) highlighted outcomes of TIVO-3 patients who received prior axitinib therapy, now commonly part of front-line advanced RCC treatment. Of this group, patients treated with tivozanib (n=83) demonstrated a median progression free survival (PFS) of 5.5 months compared to 3.7 months for those treated with sorafenib (n=89) (Hazard Ratio of 0.68), with an overall response rate of 13% and 8%, respectively. In addition, prior axitinib therapy did not appear to influence tivozanib tolerability, with adverse events, including dose reductions, interruptions, and discontinuations, similar in patients treated with and without prior axitinib therapy. These results suggest that tivozanib, a selective VEGF TKI, is active following prior axitinib therapy and can potentially provide superior PFS benefit compared to sorafenib, a multi-targeted VEGF TKI.
A copy of each presentation will be available in the Scientific Publications & Presentations section of AVEO’s website.

About Tivozanib (FOTIVDA)

Tivozanib is an oral, once-daily, next-generation VEGF TKI discovered by Kyowa Kirin Co. and approved as FOTIVDA for the treatment of adult patients with advanced RCC in the European Union and other countries in the territory of the Company’s partner, EUSA Pharma (UK) Limited (EUSA territory). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for adult patients with relapsed or refractory advanced RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.4 Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers. Tivozanib is also being studied by partner Kyowa Kirin Co. in non-oncology indications.

Kadmon Announces Pricing of $200 Million Convertible Senior Notes Offering with 100% Capped Call Transactions

On February 11, 2021 Kadmon Holdings, Inc. (Nasdaq:KDMN) reported the pricing of $200 million aggregate principal amount of 3.625% convertible senior notes due 2027 (the "Notes") in a private offering to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (Press release, Kadmon, FEB 11, 2021, View Source [SID1234574948]). This offering was upsized from the previously announced offering of $150 million of aggregate principal amount of Notes and included 100% capped call transactions. Kadmon also granted the initial purchaser of the Notes a 13-day option to purchase up to an additional $40 million aggregate principal amount of the Notes, solely to cover over-allotments. The sale of the Notes is expected to close on February 16, 2021, subject to customary closing conditions.

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The Notes will mature on February 15, 2027, unless earlier converted, redeemed or repurchased and will be convertible, subject to the satisfaction of certain conditions, into cash, shares of Kadmon’s common stock or a combination thereof as elected by Kadmon in its sole discretion. The Notes will be general unsecured obligations of Kadmon and interest will be payable semi-annually in arrears. Kadmon will have the right to redeem the Notes, in whole or in part, and from time to time, on or after February 20, 2024, subject to certain conditions, at a cash redemption price equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

The initial conversion rate of the Notes will be 143.7815 shares of Kadmon’s common stock per $1,000 principal amount of Notes (equivalent to an initial conversion price of approximately $6.96 per share). The initial conversion price of the Notes represents a premium of approximately 30% over the closing price of Kadmon’s common stock on the Nasdaq Global Select Market on February 10, 2021. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events.

If a "fundamental change" (as defined in the indenture governing the Notes) occurs, then subject to certain conditions and limited exceptions, holders may require Kadmon to repurchase their Notes at a cash repurchase price equal to 100% of the principal amount of the Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. In addition, upon certain corporate events that occur prior to the maturity date of the Notes or if Kadmon delivers a redemption notice in respect of some or all of the Notes, Kadmon will, under certain circumstances, increase the conversion rate of the Notes for holders who elect to convert their Notes in connection with such a corporate event or convert their Notes called for redemption during the related redemption period, as the case may be.

In connection with the pricing of the Notes, Kadmon entered into capped call transactions with one or more financial institutions (the "option counterparties"). The cap price of the capped call transactions relating to the Notes will initially be approximately $10.70 per share, which represents a premium of approximately 100% over the last reported sale price of Kadmon’s common stock on the Nasdaq Global Select Market on February 10, 2021, and is subject to certain adjustments under the terms of the capped call transactions.

The capped call transactions cover, subject to customary adjustments, the number of shares of common stock initially underlying the Notes. The capped call transactions are expected to generally reduce the potential dilutive effect on Kadmon’s common stock upon conversion of the Notes or at Kadmon’s election (subject to certain conditions) offset any cash payments Kadmon is required to make in excess of the aggregate principal amount of converted Notes, with such reduction and/or offset subject to a cap.

In connection with establishing their initial hedges of the capped call transactions, the option counterparties or their respective affiliates expect to enter into various derivative transactions with respect to Kadmon’s common stock and/or purchase shares of Kadmon’s common stock concurrently with or shortly after the pricing of the Notes (and, if applicable, the exercise by the initial purchaser of its over-allotment option). This activity could increase (or reduce the size of any decrease in) the market price of Kadmon’s common stock or the Notes at that time. In addition, the option counterparties or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Kadmon’s common stock and/or purchasing or selling Kadmon’s common stock or other securities issued by Kadmon 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 of 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, or following any early termination of any portion of the capped call transactions in connection with any repurchase, redemption or early conversion of the Notes). This activity could also cause or avoid an increase or a decrease in the market price of Kadmon’s common stock or the Notes, which could affect a noteholder’s ability to convert the Notes and, to the extent the activity occurs during any observation period related to a conversion of the Notes, it could affect the number of shares and value of the consideration that a noteholder will receive upon conversion of the Notes.

In addition, if any such capped call transaction fails to become effective, whether or not this offering of the Notes is completed, the option counterparties thereto may unwind their hedge positions with respect to Kadmon’s common stock, which could adversely affect the value of Kadmon’s common stock and, if the Notes have been issued, the value of the Notes.

Kadmon estimates that the net proceeds from the offering will be approximately $194 million (or approximately $233 million if the initial purchaser exercises its over-allotment option in full), after deducting the initial purchaser’s discount and estimated offering expenses payable by Kadmon.

Kadmon intends to use a portion of the proceeds to prepare to commercialize belumosudil for chronic graft-versus-host disease in the United States, if approved; for the development of its other clinical-stage product candidates; for the discovery, research and preclinical studies of its other product candidates; and other general corporate purposes. Kadmon intends to use the balance of the net proceeds from the offering to fund the cost of entering into the capped call transactions described above. In addition, if the initial purchaser exercises its over-allotment option, then Kadmon intends to use a portion of the additional net proceeds for general corporate purposes as described above and to fund the cost of entering into the capped call transactions.

Cantor Fitzgerald & Co. is acting as sole book runner for the offering. Mizuho Securities is acting as lead manager and H.C. Wainwright & Co., Oppenheimer & Co. and Raymond James are acting as co-managers for the offering.

This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities of Kadmon. Any offers of the Notes will be made only by means of a private offering memorandum. The offer and sale of the Notes and any shares of Kadmon’s common stock issuable upon conversion of the Notes have not been, and will not be, registered under the Securities Act or the securities laws of any other jurisdiction, and the Notes and such shares may not be offered or sold in the United States absent registration or an applicable exemption from the Securities Act and applicable state laws.

BIOGEN ANNOUNCES THE EXPIRATION DATE RESULTS OF ITS PRIVATE EXCHANGE OFFER

On February 11, 2021 Biogen Inc. ("Biogen") (Nasdaq: BIIB) reported the expiration date results of its previously announced private offer to exchange (the "Exchange Offer") any and all of its outstanding 5.200% Senior Notes due 2045 (the "Old Notes"), totaling $1.75 billion in aggregate principal amount, for a new series of 3.250% senior notes due 2051 to be issued by Biogen (the "New Notes") and cash on the terms and subject to conditions set forth in the Offering Memorandum dated February 4, 2021 (the "Offering Memorandum") and the accompanying eligibility letter (the "Eligibility Letter"), Canadian beneficial holder form and notice of guaranteed delivery (collectively, the "Exchange Offer Documents") (Press release, Biogen, FEB 11, 2021, View Source [SID1234574947]).

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The Exchange Offer expired at 5:00 p.m., New York City time, on February 10, 2021 (the "Expiration Date"). The "Settlement Date" will be promptly following the Expiration Date and is expected to be February 16, 2021.

The following table sets forth the aggregate principal amount of Old Notes validly tendered and not validly withdrawn at or prior to the Expiration Date, including the aggregate principal amount tendered pursuant to the guaranteed delivery procedures described in the Offering Memorandum at or prior to the Expiration Date, which Biogen expects to accept on the Settlement Date in connection with the Exchange Offer.

(1) Excluding Old Notes tendered pursuant to guaranteed delivery procedures.

These amounts are based on information provided by the Exchange Agent (as defined below) as of the Expiration Date. Upon the terms and subject to the conditions set forth in the Exchange Offer Documents, on the Settlement Date, Eligible Holders (as defined below) who (i) validly tendered and did not validly withdraw Old Notes at or prior to the Expiration Date or (ii) delivered a valid notice of guaranteed delivery and all other required documents at or prior to the Expiration Date and tender their Old Notes at or prior to 5:00 p.m., New York City time, on February 12, 2021 (the "Guaranteed Delivery Date"), pursuant to certain guaranteed delivery procedures, and whose Old Notes are accepted for exchange by Biogen, will receive the Total Exchange Consideration (as defined in the Offering Memorandum), as well as accrued and unpaid interest on such Old Notes from the last interest payment date to, but excluding, the Settlement Date.

Based on the foregoing tenders, Biogen expects to issue approximately $721 million in aggregate principal amount of New Notes, which will mature on February 15, 2051, and will bear interest at a rate per annum of 3.250%, and to pay an aggregate of approximately $156 million in cash as part of the Total Exchange Consideration, in each case assuming that all Old Notes tendered pursuant to the guaranteed delivery procedures will be tendered at or prior to the Guaranteed Delivery Date. Biogen will not receive any cash proceeds from the Exchange Offer. The actual aggregate principal amount of New Notes that will be issued and cash that will be paid on the Settlement Date is subject to change based on deliveries under the guaranteed delivery procedures and final validation of tenders.

Biogen will deliver New Notes and cash in exchange for Old Notes accepted for exchange in the Exchange Offer on the Settlement Date. Interest on the Old Notes accepted for exchange in the Exchange Offer, including those tendered pursuant to the guaranteed delivery procedures, will cease to accrue on the Settlement Date. Interest on the New Notes will accrue from the Settlement Date.

Biogen also announced today the expiration date results of its separate cash tender offer (the "Cash Offer"), made only to Ineligible Holders (as defined below), to purchase Old Notes for cash.

The complete terms and conditions of the Exchange Offer are set forth in the Exchange Offer Documents, which were distributed to Eligible Holders in connection with the Exchange Offer. The conditions to the Exchange Offer have been satisfied as of the Expiration Date.

The Exchange Offer was made only to "Eligible Holders," which are holders of Old Notes that certified that they are "qualified institutional buyers", as that term is defined in Rule 144A under the U.S. Securities Act of 1933, as amended (the "Securities Act"), or that are non-U.S. persons, as that term is defined in Rule 902 under the Securities Act (other than "retail investors" in the European Economic Area or the United Kingdom, and investors in any province or territory of Canada that are individuals or that are institutions or other entities that do not qualify as both "accredited investors" and "permitted clients"), as more fully described in the Eligibility Letter. All holders of Old Notes who are not Eligible Holders are "Ineligible Holders".

The Exchange Offer and the issuance of the New Notes have not been registered under the Securities Act, under any other federal, state or other local law pertaining to the registration of securities, or with any securities regulatory authority of any state or other jurisdiction. The New Notes may not be offered or sold except pursuant to registration or an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any applicable state securities laws.

Only Eligible Holders who submitted a valid eligibility letter were authorized to receive or review the Offering Memorandum or to participate in the Exchange Offer. For Canadian Eligible Holders, participation in the Exchange Offer was also conditioned upon the completion and return of the Canadian beneficial holder form.

Global Bondholder Services Corporation is serving as the exchange agent and information agent for the Exchange Offer (the "Exchange Agent"). Questions or requests for assistance related to the Exchange Offer may be directed to Global Bondholder Services Corporation (866) 470-3900 (U.S. toll-free) or (212) 430-3774 (collect for banks and brokers), or via e-mail at [email protected]. You may also contact your broker, dealer, commercial bank, trust company or other nominee for assistance concerning the Exchange Offer.

This news release is not an offer to sell or buy or a solicitation of an offer to buy or sell any of the securities described herein. The Exchange Offer was made solely by the Exchange Offer Documents and only to such persons and in such jurisdictions as was permitted under applicable law and the terms and conditions of the Exchange Offer.

i2O Therapeutics Announces Research Collaboration with Sanofi to Enable Oral Delivery of Nanobody-based Medicines

On February 11, 2021 i2O Therapeutics reported a research collaboration with Sanofi to investigate the oral delivery of Sanofi’s Nanobody-based medicines, which are currently administered through intravenous or subcutaneous injections (Press release, Sanofi, FEB 11, 2021, View Source [SID1234574944]).

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Nanobodies – proprietary therapeutic proteins based on camelid-derived immunoglobulin single variable domains – have potential uses in the treatment of a range of serious and life-threatening diseases and are being developed in many therapeutic areas including inflammation, hematology, immuno-oncology, oncology and rare diseases. The research collaboration between i2O Therapeutics and Sanofi will explore a new oral route of administering nanobodies.

"Our mission at i2O Therapeutics is to develop safe and effective oral formulations of therapies traditionally limited to injections and we are excited to partner with Sanofi to advance this mission," said Ravi Srinivasan, co-founder and director of i2O Therapeutics.

"i2O’s ionic liquid platform opens new opportunities to orally deliver biologics, and nanobodies represent an exciting application of this platform," said Samir Mitragotri, co-founder of i2O Therapeutics.

i2O Therapeutics announced seed funding in April 2020, which was led by Sanofi Ventures, the corporate venture capital arm of Sanofi, and JDRF T1D Fund. The company also announced a strategic investment from Colorcon Ventures, the corporate venture capital fund of Colorcon, Inc. in December 2020.