On December 11, 2019 IASO Biotherapeutics (IASO Bio), a clinical-stage biotechnology company advancing the development of innovative therapies for cancer, reported that had the latest clinical data presented on their potential best-in-class therapy at the "Efficacy and Safety of Fully Human BCMA Targeting CAR T Cell Therapy in Relapsed Refractory Multiple Myeloma" session during the prestigious 61st Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition, December 7-10 in Orlando, FL (Abstract #582) (Press release, IASO BioMed, DEC 11, 2019, View Source [SID1234552273]).

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In an IIT study conducted by Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, the oral presentation highlighted the impressive safety, efficacy and persistence of CT103A, an anti-BCMA CAR-T for the treatment of Relapsed/Refractory Multiple Myeloma. With 17 of the 18 patients evaluable, the objective response rate (ORR) was 100%. In addition, 70.6% of patients achieved a best response of stringent complete or complete response (sCR/CR), and 88.2% achieved a best response of very good partial response (VGPR) or better. CRS occurred in 17 of 18 patients (Grade 1&2- 72.2% (13), Grade 3- 16.7% (3), Grade 4- 5.6% (1)), but was generally manageable with no neurotoxicity. At the lowest dose (1 x106 cells/kg), CT103A still maintained 100% ORR, with 78% of these patients achieving a best response of very good partial response (VGPR) or better. As well, toxicity was manageable with 88% of these patients experiencing grade 2 CRS or less.

In addition, 4 patients participating in the study had relapsed from a prior murine CAR-T infusion. Their response, and the overall performance, suggests that CT103A may also provide patients, having relapsed from a prior CAR-T, a potential first-line treatment option

"Having presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) earlier this year, our presence at ASH (Free ASH Whitepaper) marks the end of a very exciting year for IASO BIO. We are very happy to see the prolonged patient response to this therapy and look forward to starting our phase II clinical trial early in the new year," said Hu Guang, Ph.D., Director of R&D at IASO BIO. "By applying highly innovative science in our pre-clinical programs, we believe our pipeline has potential to bring us closer to addressing critical unmet needs, not just for patients, but for the healthcare professionals that treat them."

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems and bone fractures. With a global annual incidence rate of 2/100,000 persons, it is one of the most commonly diagnosed blood cancers, second only to non-Hodgkin lymphoma.

This past September CT103A received IND approval for Ib/II chimeric protocol by the National Medical Products Association (NMPA), and phase II clinical trials are expected to begin in early 2020.

About Relapsed/Refractory Multiple Myeloma

For newly treated patients with multiple myeloma, common first-line treatment drugs include proteasome inhibitors, immunoregulatory drugs and alkane agents. For most patients, the commonly used first-line treatment can stabilize the patient’s condition for 3-5 years, but a small number of patients show primary drug resistance at the time of initial treatment, and the disease cannot be effectively controlled. Relapse patients are those who have a reoccurrence after complete remission of the disease. Refractory patients are those with primary drug resistance or those who have finished first-line treatment and do not achieve remission, or patients whose disease progress within 60 days after achieving minimal response. With effective treatment, the majority of patients will inevitably enter the stage of relapse and refractory after 3-5 years of disease stabilization. For these patients, the overall effective rate of existing second-line treatment is about 40% to 70%, with short remission time.

About CT103A

CT103A is an innovative therapy co-developed by IASO BIO and Innovent. Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, CT103A has been developed. A lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the CT103A CAR-T is potent and persistent.

On December 11, 2019 Ionis Pharmaceuticals, Inc. (the "Company") reported that it entered into separate privately negotiated exchange and/or subscription agreements with certain new investors and certain of the holders of its 1.00% Convertible Senior Notes due 2021 (the "2021 Notes") to exchange $375.6 million in aggregate principal amount of the Company’s 2021 Notes (the "Exchange Transactions") for $439.4 million in aggregate principal amount of the Company’s 0.125% Convertible Senior Notes due 2024 (the "Notes"), and to issue and sell an additional $109.5 million in aggregate principal amount of the Notes (the "Subscription Transactions" and, together with the Exchange Transactions, the "Transactions") (Filing, 8-K, Ionis Pharmaceuticals, DEC 11, 2019, View Source [SID1234552570]).

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On December 19, 2019 and December 20, 2019, the Company issued a total of $548.8 million aggregate principal amount of Notes in the Transactions. The Notes are general unsecured obligations of the Company and bear interest at a fixed rate of 0.125% per year, payable semiannually in arrears on June 15 and December 15 of each year, beginning on June 15, 2020. The Notes are convertible under certain circumstances and may be settled as described below. The conversion rate is initially 12.0075 shares of the Company’s common stock per $1,000 principal amount of Notes (equivalent to an initial conversion price of approximately $83.28 per share of the Company’s common stock). The conversion rate and the corresponding conversion price will be subject to adjustment in some events but will not be adjusted for any accrued and unpaid interest. In addition, if certain corporate events occur prior to the maturity date, the Company will increase the conversion rate for a holder who elects to convert its Notes in connection with such a corporate event in certain circumstances. The Company may not redeem the Notes prior to maturity, and no sinking fund is provided for the Notes. The Notes will mature on December 15, 2024, unless earlier converted or purchased.

The Company did not receive any cash proceeds from the Exchange Transactions. In exchange for issuing the Notes pursuant to the Exchange Transactions, the Company received and cancelled the exchanged 2021 Notes. The Company estimates the net proceeds from the Subscription Transactions were approximately $99.2 million after deducting estimated offering expenses for the Transactions. The Company used a portion of the net cash proceeds from the Subscription Transactions to pay the costs of the previously disclosed convertible note hedge transactions and intends to use the remaining net cash proceeds for general corporate purposes.

Indenture

The Company issued the Notes pursuant to an indenture, dated as of December 19, 2019 (the "Indenture"), by and between the Company and U.S. Bank National Association, as trustee.

Holders of the Notes may convert their Notes at their option at any time prior to the close of business on the business day immediately preceding August 1, 2024 only under the following circumstances: (1) during any calendar quarter commencing after March 31, 2020 (and only during such calendar quarter), if the last reported sale price of the Company’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day; (2) during the five business day period after any five consecutive trading day period (the "measurement period") in which the trading price per $1,000 principal amount of Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of the Company’s common stock and the conversion rate on each such trading day; or (3) upon the occurrence of specified corporate events. On or after August 1, 2024 until the close of business on the second scheduled trading day preceding the maturity date, holders of the Notes may convert their Notes at their option at the conversion rate then in effect at any time irrespective of the foregoing conditions. The Company will settle conversions of Notes by paying and/or delivering, as the case may be, cash, shares of the Company’s common stock, or a combination of cash and shares of the Company’s common stock, at its election, as described in the Indenture.

The Company may not redeem the Notes prior to maturity and no ‘‘sinking fund’’ is provided for the Notes, which means that the Company is not required to redeem or retire the Notes periodically.

If the Company undergoes a fundamental change (as defined in the Indenture), subject to certain conditions, holders of the Notes may require the Company to purchase for cash all or part of their Notes in principal amounts of $1,000 or a multiple thereof, at a purchase price equal to 100% of the principal amount of the Notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date.

The Notes are the Company’s general unsecured obligations and rank senior in right of payment to any of the Company’s indebtedness that is expressly subordinated in right of payment to the Notes; equal in right of payment with any of the Company’s liabilities that are not so subordinated (including the 2021 Notes); effectively junior in right of payment to any of the Company’s secured indebtedness to the extent of the value of the assets securing such indebtedness; and structurally junior to all indebtedness and other liabilities (including trade payables) of the Company’s subsidiaries.

The events of default, which may result in the acceleration of the maturity of the Notes, include, among other things:

failure to pay interest on the Notes when due and the continuance of such default for a period of 30 days;

failure to pay the principal on the Notes when due;

failure to comply with the Company’s obligation to convert the Notes in accordance with the Indenture upon exercise of a holder’s conversion right and such failure continues for a period of three (3) business days;

failure to provide timely notice of a fundamental change or a specified corporate transaction;

failure by the Company to comply with its obligations under the Notes or the Indenture for a period of 60 days after notice if given in accordance with the Indenture;

certain defaults under loan agreements or other instruments (other than the Indenture) evidencing indebtedness for borrowed money of the Company or any significant subsidiary of the Company in excess of $100 million; and

certain events of bankruptcy or insolvency involving the Company or any significant subsidiary of the Company.

On December 11, 2019 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that positive frontline data for naxitamab will be presented at the Company’s R&D event, which takes place in New York City today at 12 p.m. Eastern (Press release, Y-mAbs Therapeutics, DEC 11, 2019, View Source [SID1234552257]). Key opinion leaders, including Dr. Shakeel Modak, M.D., MRCP and Dr. Kim Kramer, M.D., both from Memorial Sloan Kettering Cancer Center ("MSK") and Dr. Jaume Mora, M.D., Ph.D. from SJD Barcelona Children’s Hospital, will discuss the current treatment landscape and unmet medical needs for high-risk neuroblastoma and other solid tumors. Members of the media and public may access the event via a live webcast.

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Dr. Mora, who has experience treating frontline neuroblastoma patients with both naxitamab and a competing anti-GD2 antibody, will present clinical data from both antibodies. Data from an investigator sponsored frontline study of 34 patients with high-risk stage 4 neuroblastoma in first complete remission showed a 72% event free survival at 24 months for naxitamab patients, which compared favorably to the 63% reported at 24 months for a population of 89 patients treated with a competing anti-GD2 antibody. In addition, it was noted that only 20% of the patients treated with naxitamab received bone marrow transplant, as was the case for all patients treated with the competing anti-GD2 antibody. In terms of overall survival ("OS"), the naxitamab patients achieved an 86% OS at 24 months, compared to 84% OS for the competing anti-GD2 antibody.

The naxitamab treatment was well-tolerated, and the infusion related pain generally associated with anti-GD2 antibodies required significantly less opioids for naxitamab than for the competing anti-GD2 antibody. The use of morphica generally declined significantly after the first treatment cycle, and naxitamab required less than 15% of the morphine dose required by the competing anti-GD2 antibody. A second frontline study with naxitamab is currently ongoing at MSK in New York City, and Y-mAbs expects data from this study to be published in the first half of 2020. Y-mAbs is also planning a multicenter frontline study, which we expect to initiate in 2020.

"I am delighted and excited to welcome this excellent group of key opinion leaders to our R&D Event. It will be a great opportunity to learn more about the clinical experience of both naxitamab and omburtamab, also noting that SJD Barcelona Children’s Hospital, a major pediatric center located in Barcelona, Spain, has produced very encouraging frontline naxitmab data," said Thomas Gad, Founder, Chairman, President and Head of Business Development and Strategy.

Dr. Claus Moller, Chief Executive Officer further notes, "We are excited to share the first ever frontline data from naxitamab, and believe this to be class leading clinical results. The reduced use of morphica and the convenience of giving naxitamab in an outpatient setting, shows the important role naxitamab has in addressing the clear unmet medical needs of children waiting for new treatment options."

MSK has institutional financial interests with Y-mAbs in the form of equity and intellectual property interests through licensing agreements.

On December 11, 2019 Omega Funds, a leading international investment firm focused on delivering impactful medicines to patients, reported the closing of Omega Fund VI, L.P. ("Fund VI"), with $438 million in capital commitments (Press release, Omega Fund Management, DEC 11, 2019, View Source [SID1234552274]). With Fund VI, the firm will continue to execute on its strategy of creating and investing in life sciences companies that target the most urgent medical needs. Since its inception in 2004, Omega Funds has raised more than $1 billion to invest in exceptional entrepreneurs developing innovative products across multiple therapeutic areas, including oncology, immunology, rare diseases, precision medicine and others.

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Omega Funds has a strong track record of identifying and supporting great management teams and companies by providing domain knowledge and perspective, network connectivity, and capital. Omega Funds’ portfolio companies have brought 37 new products to market and the firm’s investments have contributed to 24 successful portfolio company IPOs and 35 portfolio company exits via M&A.

"We appreciate the trust from our limited partners and their support of our distinctive investment style, which is guided by our conviction in people, products and breakthrough ideas, not by conventional categories," said Otello Stampacchia, Ph.D., Managing Director of Omega Funds. "Fund VI builds on our modus operandi aimed at investing in and, in many cases, actively combining innovative science with exceptional founders and company builders."

Fund VI is stage-agnostic and is expected to be deployed across companies in the U.S. and Europe. Similar to past funds, Fund VI investments will include a variety of investment approaches, from company founding and creation to early venture rounds and late-stage public investing, as well as direct secondary transactions.

"We believe this is the most exciting time to be investing in life sciences in a generation, but it requires diverse skills to capture the opportunity set," added Dr. Stampacchia. "At Omega, we have thoughtfully assembled a team that has the experience, insights and connections needed to successfully identify and harvest innovation from both sides of the Atlantic."

Omega Funds also announced today that industry veteran Bernard Davitian will be joining the firm as a Partner, beginning January 2020. Recent additions to the Omega Funds team also include Deirdre Cunnane, J.D., who joined as Chief Operating Officer and General Counsel in October 2019, as well as Paulina Hill, Ph.D., who joined as Principal, and Katie Kerfoot, who joined as head of Investor Relations, both of whom joined in January 2019.

Mr. Davitian has extensive experience in the life sciences and biotech industry, marked by a number of successful transactions involving financings and M&A. He previously served as SVP and Managing Director at Sanofi Ventures, having first joined Sanofi in 2010 as Vice President, Deputy Global Head, Business Development. Prior to Sanofi, Mr. Davitian held leadership roles at Fovea Pharmaceuticals, which was sold to Sanofi in 2009 in a €370 million cash transaction, Neurotech Pharmaceuticals, Transgene, which successfully raised $100 million in a 1998 IPO on the NASDAQ and EuroNext, as well as Institut Mérieux (now Sanofi Pasteur).

Ms. Cunnane, COO & GC, has held similar roles both in venture funds and within a biotech company. She joins Omega Funds from Catabasis Pharmaceuticals, a publicly traded biotech company where she held various leadership positions over the past four years. Prior to joining Catabasis, Ms. Cunnane served as General Counsel at Advanced Technology Ventures and Lightstone Ventures.

Prior to joining Omega Funds, Dr. Hill was on the healthcare team at Polaris Partners since 2012. She completed her postdoctoral fellowship in Robert Langer’s lab in the Chemical Engineering department at the Massachusetts Institute of Technology and earned her Ph.D. in Molecular Medicine from the Wake Forest University School of Medicine.

Ms. Kerfoot joined Omega Funds to lead the firm’s communications strategy and investor relations initiatives, including marketing and fundraising. Prior to joining Omega Funds, she covered specialty pharmaceutical companies as an equity research analyst at Wells Fargo Securities and BMO Capital Markets in New York. Ms. Kerfoot has an extensive journalism background, including on-air reporting with an NBC-affiliate local news station and a national online news network.

On December 11, 2019 Kite, a Gilead Company (Nasdaq: GILD), reported that it has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the investigational chimeric antigen receptor (CAR) T cell therapy, KTE-X19, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Kite Pharma, DEC 11, 2019, View Source [SID1234552275]).

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The BLA submission is based on data from the Phase 2 ZUMA-2 trial, which demonstrated an overall response rate of 93 percent, including 67 percent with complete response, as assessed by an Independent Radiologic Review Committee (IRRC) following a single infusion of KTE-X19. In the safety analysis, Grade 3 or higher cytokine release syndrome (CRS) and neurologic events were seen in 15 percent and 31 percent of patients, respectively. No Grade 5 CRS or neurologic events occurred. Detailed findings from this trial were recently presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in Orlando.

"There remains a significant need for new treatments for patients with relapsed/refractory MCL despite recent advances, so this regulatory filing is an especially important milestone for the MCL community," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "We look forward to working with the FDA to bring KTE-X19 to appropriate patients as quickly as possible and continuing to deliver on the promise of our industry-leading cell therapy development program with a second CAR T therapy."

Kite plans to submit a Marketing Authorization Application for KTE-X19 in the European Union in early 2020. KTE-X19 has been granted Breakthrough Therapy Designation (BTD) by the FDA and Priority Medicines (PRIME) by the European Medicines Agency (EMA) for relapsed or refractory MCL.

KTE-X19 is investigational and not approved anywhere globally. Its efficacy and safety have not been established. More information about clinical trials with KTE-X19 is available at www.clinicaltrials.gov.

About MCL

MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the "mantle zone" of the lymph node and typically affects men over the age of 60.

About ZUMA-2

ZUMA-2 is a single-arm, multicenter, open-label Phase 2 study involving 74 enrolled/leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BTK inhibitors ibrutinib or acalabrutinib. The objectives of the study are to evaluate the efficacy (60 patients) and safety (68 patients) after a single infusion of KTE-X19 in this patient population. The primary endpoint for the study is objective response rate (ORR). ORR in this trial is defined as the combined rate of complete responses and partial responses as assessed by an IRRC.

Secondary endpoints include duration of response, progression-free survival, overall survival, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score. The study is ongoing.

About KTE-X19

KTE-X19 is an investigational, autologous, anti-CD19 CAR T cell therapy. KTE-X19 uses the XLP manufacturing process that includes T-cell selection and lymphocyte enrichment. Lymphocyte enrichment is a necessary step in certain B-cell malignancies with evidence of circulating lymphoblasts. KTE-X19 is currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).