On July 18, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported the appointment of Friedrich Graf Finckenstein, M.D., as chief medical officer (Press release, Iovance Biotherapeutics, JUL 18, 2019, View Source [SID1234537598]). Dr. Graf Finckenstein brings over 19 years of experience in clinical development and translational research to the company.

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"We are very pleased to have Dr. Finckenstein join Iovance as we move forward with pivotal studies for lifileucel in metastatic melanoma and LN-145 in metastatic cervical cancer," said Maria Fardis, Ph.D., president and chief executive officer of Iovance Biotherapeutics. "Dr. Finckenstein’s experience with prior approval of checkpoint therapy as well as his breadth of involvement with translational medicine will be of great value to Iovance while we progress our late-stage development programs toward commercialization and expand the utility of TIL in new indications."

"I am very pleased to be part of a dedicated team working on bringing a novel cell therapy to patients with very limited approved therapeutic options," commented Friedrich Graf Finckenstein, M.D. "I’m excited to be able to contribute to development of TIL therapy as we work on the important next steps involved in preparing for regulatory submission."

Dr. Graf Finckenstein is a physician-scientist with decades of experience in clinical medicine, laboratory cancer research, and drug development in the biopharmaceutical industry. Prior to joining Iovance he was Global Head of Oncology Translational Medicine at Roche Pharma Research and Early Development (pRED) in Basel, Switzerland, where he led all clinical development aspects in the Oncology Discovery and Translational Area, including the design and conduct of clinical trials, exploratory development studies and translational medicine, biomarker and personalized healthcare strategy. Prior to that, Dr. Graf Finckenstein held multiple clinical leadership roles at Bristol-Meyers Squibb Company, where he worked on an array of products from early clinical development to late stage, including key contributions to the approval of Opdivo in lung cancer. Dr. Graf Finckenstein has a medical degree from the University of Hamburg in Germany. He holds a German medical license, a pediatric board certification, and has conducted basic cancer research at the Ludwig Institute, San Diego Branch, the Children’s Hospital Los Angeles and the University of Hamburg.

On July 18, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported the pricing of its initial public offering of American Depositary Shares (ADSs) in the United States (the "Offering") and the listing of the ADSs on the Nasdaq Global Select Market under the symbol "GMAB (Press release, Genmab, JUL 18, 2019, View Source [SID1234537583])." The offering will produce gross proceeds of $505,875,000 from the sale of 2,850,000 ordinary shares of Genmab in the form of 28,500,000 ADSs at a price of $17.75 per ADS. Each ADS will represent one-tenth of one ordinary share of Genmab. In addition, Genmab has granted the underwriters an option to purchase up to 4,275,000 additional ADSs, representing 427,500 ordinary shares to cover any over-allotments (the "Option"). The Option can be exercised during the 30-day period commencing July 17, 2019.

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In connection with the anticipated listing of our ADSs on the Nasdaq Global Select Market, we have requested that Nasdaq Copenhagen change the symbol for our ordinary shares from "GEN" to "GMAB" to become effective in connection with the admission to trading of the ordinary shares underlying the ADSs on Nasdaq Copenhagen, expected to occur on July 23, 2019.

Summary of the Offering:

The Offering will consist of an offering of a total of 28,500,000 ADSs, corresponding to 2,850,000 underlying ordinary shares of Genmab (the "New Shares"), which in their entirety are expected to be subscribed for by BofA Merrill Lynch, Morgan Stanley and Jefferies (the "Joint Book-Running Managers"), as representatives of the several underwriters, with an instruction to deliver such new shares to Deutsche Bank Trust Company Americas acting as depositary for the underlying New Shares in the Offering;
The public offering price is $17.75 per ADS, corresponding to a subscription price of DKK 1,181.80 per underlying ordinary share at an exchange rate of DKK 6.6580 per US$1.00 on July 17, 2019, multiplied by the ADS-to-share ratio of 10 to 1;
The Joint Book-Running Managers, as representatives of the several underwriters, have been granted an Option to acquire an additional 4,275,000 ADSs, exercisable in whole or in part through August 16, 2019 to cover over-allotments.
The New Shares underlying the ADSs will correspond to 4.4% of Genmab’s entire share capital assuming no exercise of the Option and 5.0% of Genmab’s entire share capital assuming full exercise of the Option;
Gross proceeds from the Offering will amount to $505.9 million (DKK 3,368.1 million) assuming no exercise of the Option and $581.8 million (DKK 3,873.3 million) assuming full exercise of the Option;
Allocation of the ADSs has been determined by the board of directors in consultation with the Joint Book-Running Managers; and
A timetable of expected future principal events can be seen below:
Event Expected date
The ADSs start trading on the Nasdaq Global Select Market… July 18, 2019
Filing in the United States of the final prospectus …………….. July 18, 2019
Closing of the Offering …………………………………………… July 22, 2019
Registration of the New Shares underlying the ADSs
with the Danish Business Authority ……………………………..

July 22, 2019
Admission for listing of the New Shares underlying the
ADSs on Nasdaq Copenhagen ……………………………………..

July 23, 2019
In addition, Genmab announced that the board of directors of Genmab has today determined (i) to increase the size of the Offering from up to 27,800,000 ADSs to a total of 28,500,000 ADSs, and to issue a total of 28,500,000 ADSs (excluding any ADSs that may be sold or issued as part of the Option (as defined below)) and 2,850,000 underlying new Genmab shares, and (ii) that the public offering price for the ADSs issued as part of the Offering is $17.75 per ADS, corresponding to a subscription price of DKK 1,181.80 per underlying share issued at an exchange rate of DKK 6.6580 per US$1.00 on July 17, 2019. In connection with the pricing of the Offering the board of directors of Genmab has today decided to repeal the decision of July 9, 2019 to exercise its authorization to increase the share capital by up to 3,197,000 new shares underlying the ADSs and simultaneously in accordance with article 4A of Genmab’s articles of association exercised an authorization granted by Genmab’s annual general meeting held on April 10, 2018, to increase Genmab’s share capital by issue of up to 3,277,500 new shares underlying the ADSs, of which 2,850,000 cover the shares being issued in connection with the Offering and 427,500 will cover shares in case the Option is exercised.

The registration statement on Form F-1 relating to the ADSs, including the preliminary prospectus forming a part thereof, has been declared effective by the U.S. Securities and Exchange Commission (the "SEC"). The offering of the ADSs is being made only by means of such prospectus.

BofA Merrill Lynch, Morgan Stanley and Jefferies are acting as joint book-running managers for the Offering. Guggenheim Securities and RBC Capital Markets are acting as joint lead-managers and Danske Markets, H.C. Wainwright & Co. and Kempen are acting as co-managers for the Offering. A copy of the preliminary prospectus and, when available, the final prospectus relating to the Offering may be obtained from BofA Merrill Lynch, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department, or by email: [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014; or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone: 1-877-821-7388, or by email: [email protected]. Copies of the preliminary prospectus and, when available, the final prospectus related to the Offering are also available, or will be available, at www.sec.gov. No Danish prospectus will be issued or offered.
This Company Announcement does not constitute an offer to sell nor a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On July 18, 2019 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported it has received the approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with a Phase 1/2a clinical trial of TG6002 administered by intrahepatic artery (IHA) infusion in colorectal cancer patients with unresectable liver metastases (CRLM) (Press release, Transgene, JUL 18, 2019, View Source [SID1234537599]).

TG6002 is a next-generation oncolytic virus (OV), which has multiple mechanisms of action. It has been engineered to combine the killing of cancer cells (oncolysis), the production of 5-FU, a widely used chemotherapeutic agent, in the tumor site, and the eliciting of an immune response against tumor cells. TG6002 expresses the proprietary FCU1 gene in the cancer cells it has infected, leading to local conversion of the pro-drug 5-FC (administered orally) into 5-FU. This is particularly important as most gastrointestinal tumors are 5-FU sensitive. TG6002 has been shown to induce both response in the primary tumor and an immune-mediated regression of distant metastases in preclinical experiments1.

"Current systemic therapies prolong survival of CRLM patients at the cost of significant side effects. We believe that TG6002 therapy administered via an IHA infusion potentially offers an additional effective and well tolerated treatment modality for these difficult to treat patients. By administering it via the intrahepatic artery, we believe we can conveniently deliver more concentrated doses of TG6002 to the tumor, to achieve better outcomes for unresectable colorectal cancer, whilst limiting systemic exposure. In parallel, Transgene is conducting a Phase 1/2 trial to investigate TG6002 in colorectal cancer patients when given intravenously," said Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

Dr. Adel Samson, MB ChB PhD, Medical Oncologist at St. James’ University Hospital, is the Chief Investigator of the trial.
This trial is a single-arm open-label Phase 1/2a trial evaluating the safety, pharmacokinetics and efficacy of repeated and ascending doses of TG6002 administered by IHA route in combination with oral 5-FC, a non-cytotoxic pro-drug that can be converted in 5-FU. The study is expected to start in Q4 2019 and could enroll up to 75 patients.

— End–

About TG6002
TG6002 is a next generation oncolytic immunotherapy. It has been designed to induce the breakdown of cancer cells (oncolysis) and allow the local production of chemotherapy (5-FU) in the tumor. TG6002 is a modified Vaccinia virus, with double gene deletion (TK-RR-), and expressing the proprietary FCU1 gene in the cancer cells it has infected, leading to the local conversion of the non-cytotoxic pro-drug, flucytosine (5-FC), into 5-FU, a widely used cancer chemotherapy. The oncolytic virus TG6002 has shown efficacy and good safety profile in several preclinical models. Transgene believes that TG6002 may represent a new therapeutic option in recurrent cancer patients.
Another Phase 1/2 trial using TG6002 administered intravenously is ongoing in Europe in patients with advanced gastrointestinal tumors.

About Colorectal cancer
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in Europe and a leading cause of death both in Europe and worldwide. In 2012, there were 447,000 new cases of CRC in Europe with 215,000 deaths and worldwide, there were 1.4 million new cases with 694,000 deaths (Ferlay J. et al., 2013, Ferlay J. et al., 2015). Approximately half of all CRC patients develop liver metastases, only a small proportion of whom being suitable for potentially curative hepatic resection (Leporrier J, 2006). Over the last decade, the clinical outcome for patients with metastatic CRC (mCRC) has improved. Today, the median overall survival (OS) for patients with mCRC is ∼30 months.

On July 18, 2019 Kronos Bio, Inc. (Kronos), a Two River portfolio company, reported it has closed a $105 million Series A Preferred Stock financing (Press release, Kronos Bio, JUL 18, 2019, View Source [SID1234537600]). The financing was led by Vida Ventures, LLC and Omega Funds and included participation from Nextech, GV (formerly Google Ventures), Perceptive Advisors, Invus and Polaris Partners. This Series A round also included significant participation from Kronos’ President and Chief Executive Officer, Norbert Bischofberger, Ph.D. as well as members of the Board of Directors including Arie Belldegrun, M.D., FACS and John Martin, Ph.D. In conjunction with this financing, Jakob Loven, Ph.D., Partner at Nextech, will join the Board of Directors of Kronos Bio.

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Kronos’ Small Molecule Microarray platform (SMM) was built on more than a decade of research by its scientific founder, Angela Koehler, Ph.D., Associate Professor of Biological Engineering at the Massachusetts Institute of Technology. SMM is ideally suited for the rapid discovery of novel modulators or degraders of historically undruggable targets, such as transcription factors. Kronos has demonstrated SMM’s potential to identify compounds that bind to target proteins directly or interfere at nanomolar potency with protein activity. SMM enables discovery of hits that act through a variety of mechanisms, including disruption of protein-protein or protein-DNA interactions, or indirect modulation of target protein activity by binding to co-factors or other protein complex members.

"We are excited to have the continued support of high caliber investors who recognize the potential of Kronos’ technology and its team. This financing will help us advance two preclinical programs built upon hits identified from SMM screens, accelerate our research, and further expand the Kronos team in the Boston and San Francisco areas," said Norbert Bischofberger, Ph.D., President and Chief Executive Officer of Kronos. "We seek to challenge the historic belief that certain targets cannot be pursued. Our goal is to unlock new therapeutic approaches and bring treatments to areas with high unmet need."

Existing therapies target only a minority of the body’s proteins, which are well-structured and accessible to traditional small molecule approaches. The majority of proteins, however, are disordered or lack obvious binding pockets and have historically been considered undruggable. Kronos’ platform enables high-throughput screens of chemical libraries against such target proteins in a more physiologically relevant context to identify biologically active small molecules.

"When we founded Kronos at Two River, we identified early on the need for support by investors who embrace cutting edge innovation," said Joshua Kazam, a Kronos Board Member and a Director at Vida Ventures. "With this Series A round, we have expanded support with investors equally as passionate about funding scientific breakthroughs to impact how we treat some of the most challenging diseases we face today."

"Since our initial investment, we have been very excited about the opportunity to identify novel therapies provided by the Kronos platform: we believe this is a huge opportunity not just for investors but more importantly, for addressing unmet needs in hard-to-treat diseases," said Otello Stampacchia, Ph.D., a Kronos Board Member and Founder and Managing Director of Omega Funds. "We are delighted to co-lead this milestone Series A financing and to be a part of the Kronos Bio team in this journey."

On July 18, 2019 Novartis reported an exceptional first half performance in 2019 as a focused medicines company with strong sales and productivity driving double digit core operating income growth with margin expansion (Press release, Novartis, JUL 18, 2019, https://www.novartis.com/news/media-releases/novartis-delivers-strong-sales-double-digit-core-operating-income-growth-and-launches-zolgensma-and-piqray-second-quarter-sales-and-profit-guidance-increased [SID1234537585]). We increased our full year guidance for both sales and core operating income in light of our strong momentum. We continue to progress our breakthrough medicines pipeline, with the launches of Zolgensma and Piqray, and are on track for the upcoming pivotal trial results of Entresto in preserved ejection fraction heart failure, ofatumumab in multiple sclerosis, and fevipiprant in asthma."

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Financials

In order to comply with International Financial Reporting Standards (IFRS), Novartis has separated the Group’s reported financial data for the current and prior years into "continuing" and "discontinued" operations. The results of the Alcon business are reported as discontinued operations. See page 42 and Notes 2, 3 and 11 in the Condensed Interim Financial Report for a full explanation.

The commentary below focuses on continuing operations including the businesses of Innovative Medicines and Sandoz (including the US generic oral solids and dermatology portfolio), as well as the continuing Corporate functions. We also provide information on discontinued operations.

Continuing operations second quarter

Net sales were USD 11.8 billion (+4%, +8% cc) in the second quarter driven by volume growth of 10 percentage points (cc), mainly from Cosentyx, Entresto and Lutathera. Strong volume growth was partly offset by the negative impacts of pricing (-1 percentage point cc) and generic competition (-1 percentage point cc).

Operating income was USD 2.7 billion (+10%, +17% cc) mainly driven by higher sales, improved gross margin, productivity programs and higher divestment gains, partly offset by growth investments and legal provisions.

Net income was USD 2.1 billion, declining compared to prior year which benefited from a USD 5.7 billion net gain recognized from the sale of our stake in the GSK consumer healthcare joint venture. EPS was USD 0.91.

Core operating income was USD 3.6 billion (+14%, +20% cc) mainly driven by higher sales, improved gross margin and productivity programs, partly offset by growth investments. Core operating income margin was 31.0% of net sales, increasing by 2.7 percentage points (+3.2 percentage points cc).

Core net income was USD 3.1 billion (+13%, +19% cc) driven by growth in core operating income. Core EPS was USD 1.34 (+14%, +20% cc) in line with core net income.

Free cash flow from continuing operations amounted to USD 3.6 billion (+11% USD) compared to USD 3.3 billion in prior year, mainly driven by higher operating income adjusted for non-cash items, and higher divestment proceeds, partly offset by higher working capital, increased payments out of provisions and lower dividends received from the OTC JV which was divested in Q2 2018.

Innovative Medicines net sales were USD 9.3 billion (+5%, +9% cc) in the second quarter, as Pharmaceuticals grew 10% (cc) and Oncology grew 9% (cc). Volume contributed 10 (cc) percentage points to sales growth, mainly driven by Cosentyx, Entresto and Lutathera. Generic competition had a negative impact of 1 (cc) percentage point. Net pricing had a negligible impact.

Sandoz net sales were USD 2.4 billion (-1%, +3% cc) driven by volume growth of 10 percentage points (cc) partially offset by 7 percentage points (cc) of price erosion, mainly in the US. Excluding the US, net sales grew +7% (cc). Global sales of Biopharmaceuticals grew 16% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).

Novartis continues to expect the previously-announced divestment of the Sandoz US oral solids and dermatology portfolio to be completed during 2019, pending closing conditions including regulatory approvals. Novartis remains fully committed to this business until it is divested to Aurobindo. The results of this business are included in continuing operations.

Continuing operations first half

Net sales were USD 22.9 billion (+3%, +8% cc) in the first half driven by volume growth of 11 percentage points (cc), mainly from Cosentyx, Entresto and Lutathera. Strong volume growth was partly offset by the negative impacts of pricing (-2 percentage points cc) and generic competition (-1 percentage point cc).

Operating income was USD 4.9 billion (+2%, +11% cc) mainly driven by higher sales and improved gross margin, partly offset by growth investments and legal provisions.

Net income was USD 4.0 billion (-59%, -56% cc) as prior year benefited from a USD 5.7 billion net gain recognized from the sale of our stake in the GSK consumer healthcare joint venture. EPS was USD 1.72 (-59%, -55% cc) in line with net income.

Core operating income was USD 6.9 billion (12%, +19% cc) mainly driven by higher sales, improved gross margin and productivity programs, partly offset by growth investments. Core operating income margin was 30.2% of net sales, increasing by 2.4 percentage points (+2.9 percentage points cc).

Core net income was USD 5.9 billion (+9%, +16% cc) driven by growth in core operating income partly offset by the discontinuation of core income from the GSK consumer healthcare joint venture. Core EPS was USD 2.55 (+9%, +17% cc) in line with core net income.

Free cash flow from continuing operations amounted to USD 5.5 billion (+6% USD) compared to USD 5.2 billion in the prior year, mainly driven by higher operating income adjusted for non-cash items, and higher divestment proceeds, partly offset by higher working capital, a sales milestone from the divested Vaccines business received in the prior year, increased payments out of provisions and lower dividends received from the OTC JV which was divested in Q2 2018.

Innovative medicines delivered net sales of USD 18.1 billion (+5%, +10% cc) in the first half. Pharmaceuticals BU grew 10% (cc) driven by Cosentyx and Entresto. Oncology grew 9% (cc) driven by Lutathera, as well as Promacta/Revolade, Tafinlar + Mekinist and Kisqali. Volume contributed 11 (cc) percentage points to sales growth. Generic competition had a negative impact of 1 (cc) percentage point. Net pricing had a negligible impact.

Sandoz net sales were USD 4.8 billion (-4%, +1% cc) driven by volume growth of 9 percentage points (cc) partially offset by 8 percentage points (cc) of price erosion, mainly in the US. Excluding the US, net sales grew 6% (cc). Global sales of Biopharmaceuticals grew 14% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).

Discontinued operations second quarter

Discontinued operations include the business of Alcon and certain Corporate costs directly attributable to Alcon up to the spin-off date. As the Alcon spin-off was completed on April 9, 2019, the operating results in the second quarter were not material. Net income in the second quarter 2019 includes the non-taxable non-cash net gain on distribution of Alcon Inc. to Novartis AG shareholders which amounted to USD 4.7 billion. The second quarter of prior year included the results from the operations of the Alcon Division and certain Corporate costs directly attributable to Alcon with sales of USD 1.8 billion and operating income of USD 53 million. For further details see Note 3 Significant transactions – Completion of the spin-off of the Alcon business through a dividend in kind distribution to Novartis shareholders.

Discontinued operations first half

Discontinued operations net sales in the first half of 2019 were USD 1.8 billion compared to USD 3.6 billion in 2018 and operating income amounted to USD 71 million compared to USD 129 million in 2018. Net income from discontinued operations in the first half of 2019 amounted to USD 4.6 billion compared to USD 98 million in 2018 driven by the non-taxable non-cash net gain on distribution of Alcon Inc. to Novartis AG shareholders which amounted to USD 4.7 billion. For further details see Note 3 Significant transactions – Completion of the spin-off of the Alcon business through a dividend in kind distribution to Novartis shareholders.

Total Group second quarter

For the total Group, net income amounted to USD 6.8 billion compared to USD 7.8 billion in the prior year, and basic earnings per share decreased to USD 2.94 from USD 3.34. Cash flow from operating activities for the total Group amounted to USD 3.1 billion and free cash flow to USD 3.6 billion.

Total Group first half

For the total Group, net income amounted to USD 8.6 billion compared to USD 9.8 billion in the prior year, and basic earnings per share decreased to USD 3.70 from USD 4.21. Cash flow from operating activities for the total Group amounted to USD 5.5 billion and free cash flow to USD 5.4 billion.

ECN Appointment

Novartis has appointed Marie-France Tschudin as president of Novartis Pharmaceuticals. She is a member of the Executive Committee of Novartis and reports to Vas Narasimhan, CEO, Novartis.

Marie-France Tschudin has more than 25 years of broad, multi-national experience in the pharmaceuticals and biotech industry. She was most recently Head of Novartis Pharmaceuticals, Region Europe where she successfully grew the largest regional business within Novartis to over USD 8 billion in sales in 2018. She also built a diverse leadership team and oversaw the preparations for our potential blockbuster launches in Europe. Before joining Novartis, Marie-France spent 10 years at Celgene in a variety of leadership and general management positions and led their Hematology-Oncology business for Europe, Middle East and Africa.

Key growth drivers (Q2 performance)

Underpinning our financial results in the second quarter is a continued focus on key growth drivers including:

Cosentyx (USD 858 million, +25% cc) delivered strong demand driven growth in the US and all other regions. In the US, Cosentyx (USD 534 million) sales grew 31%, in the rest of the world sales grew 18% (cc).
Entresto (USD 421 million, +81% cc) delivered a strong quarter with continued growth momentum fueled by increased demand in both hospital and ambulatory settings across all territories/geographies. The Heart Failure Association of the European Society of Cardiology published a consensus paper in May that supports Entresto as a first line treatment option for patients hospitalized with HFrEF.
Lutathera (USD 109 million, USD +85 million) continued to grow led by the US with over 140 centers actively treating and the European launch progressing well. Sales from all AAA brands (including Lutathera and radiopharmaceutical diagnostic products) were USD 171 million.
Promacta/Revolade (USD 349 million, +23% cc) continued to grow at a strong double-digit rate across all regions driven by increased use in chronic immune thrombocytopenia (ITP) and uptake as first-line treatment for severe aplastic anemia (SAA) in the US and Japan.
Tafinlar + Mekinist (USD 340 million, +25% cc) continued double-digit growth due to demand in metastatic melanoma and NSCLC, and strong uptake of the adjuvant melanoma indication in the US and Europe.
Jakavi (USD 284 million, +26% cc) continued double-digit growth across all regions driven by demand in myelofibrosis and polycythemia vera indications.
Kisqali (USD 111 million, +94% cc) continued to grow in the US driven by use in first-line metastatic breast cancer patients, independent of menopausal status or combination partner, with strong uptake in Europe and other regions.
Kymriah (USD 58 million) strong demand continued and sales increased primarily driven by ongoing uptake in the US and Europe. There are over 130 qualified treatment centers and 19 countries worldwide that have coverage for at least one indication. Reimbursement for both Pediatric ALL and DLBCL was received in Japan, making Kymriah the only CAR-T available in Asia.
Biopharmaceuticals (biosimilars, biopharmaceutical contract manufacturing and Glatopa) grew 16% (cc), driven by continued strong double-digit growth in Europe from Rixathon (rituximab), Hyrimoz (adalimumab) and Erelzi (etanercept).
Emerging Growth Markets, which comprise all markets except the US, Canada, Western Europe, Japan, Australia and New Zealand, sales grew 9% in cc (1% in USD), mainly driven by double digit growth (cc) in China.

Strengthen R&D – Key developments from the second quarter

New approvals and regulatory update

Zolgensma (onasemnogene abeparvovec-xioi) was launched in the US following FDA approval. Zolgensma is approved for the treatment of patients less than 2 years of age with SMA and bi-allelic mutations of the SMN1 gene, regardless of SMN2 back-up gene copy number (all types). This also includes pre-symptomatic newborns who are diagnosed by genetic testing.
Piqray (alpelisib, formerly BYL719) was approved and launched in the US as the first and only treatment specifically for patients with a PIK3CA mutation in HR+/HER2- advanced breast cancer. Piqray was the first new drug application approved under the FDA Oncology Center of Excellence Real-Time Oncology Review pilot program.
Regulatory submissions and filings

Crizanlizumab (SEG101) was filed in the US and Europe for the prevention of vaso-occlusive crises in sickle cell disease. Crizanlizumab received priority review designation from the FDA in July.
QVM149 (ICS/LABA/LAMA) and QMF149 (ICS/LABA) were both filed with EMA for the treatment of asthma. QVM149 has the potential to become the best in class inhaled treatment by adding the power of comprehensive bronchodilation to on-target inflammation control with a once-daily inhalation.
Results from ongoing trials and other highlights

Zolgensma data were presented at AAN demonstrating efficacy in broad a spectrum of SMA patients:
STRONG trial interim data in SMA Type 2 showed rapid motor function gains and milestone achievements with intrathecal dosing
SPR1NT interim data in pre-symptomatic SMA showed age-appropriate motor milestone achievement
STR1VE interim data in SMA Type 1 continued to show event-free survival, increases in motor function and significant milestone achievement consistent with Phase 1 START trial
Kisqali MONALEESA-7 overall survival data were presented at ASCO (Free ASCO Whitepaper) in first-line treatment of advanced breast cancer exclusively in peri- and premenopausal women. The data showed a survival rate of 70.2% for patients on Kisqali combination therapy compared to 46.0% for endocrine therapy alone. Kisqali is the only CDK4/6 inhibitor to show superior overall survival in advanced breast cancer.
Capmatinib (INC280) GEOMETRY mono-1 Phase II data in patients with NSCLC that harbor MET exon-14 skipping mutation were presented at ASCO (Free ASCO Whitepaper). The overall response rate among patients receiving capmatinib was 68% for treatment-naive and 41% for previously treated patients. The median duration of response was also clinically meaningful irrespective of prior line of therapy.
Mayzent (siponimod) data from EXPAND study, presented at AAN, demonstrated that treatment had a clinically meaningful positive impact on cognitive processing speed in patients with secondary progressive MS, an important element in cognitive function. These data supplement benefits seen in terms of delay in disability progression in this population.
Iscalimab (CFZ533) data were presented at the American Transplant Congress showing 60% of iscalimab-treated transplant patients have normal kidney histology at least 1 year after transplant vs 0% with tacrolimus (current standard of care).
Cosentyx FUTURE 5 and MAXIMISE data were presented at EULAR. FUTURE 5 reinforced that there was no radiographic progression in almost 90% of psoriatic arthritis (PsA) patients treated over 2 years. MAXIMISE showed first efficacy and safety of a biologic treatment in the management of axial manifestations of PsA, which affect up to an estimated 35 million people worldwide.
Tafinlar + Mekinist overall survival data presented at ASCO (Free ASCO Whitepaper) and published simultaneously in NEJM, showed in patients with unresectable or metastatic BRAF-mutation positive melanoma, 34% of all patients in the pooled COMBI-d and COMBI-v trial analysis survived at five years. Nineteen percent of patients also showed no sign of disease progression or death at five years.
Hyrimoz (Sandoz biosimilar adalimumab) Phase III ADMYRA trial data presented at EULAR confirmed switching from reference biologic had no impact on safety or efficacy in patients with moderate-to-severe rheumatoid arthritis.
Capital structure and net debt
Retaining a good balance between investment in the business, a strong capital structure and attractive shareholder returns remains a priority.

During the first half of 2019, Novartis repurchased a total of 32.8 million shares for USD 2.8 billion on the SIX Swiss Exchange second trading line, including 19.0 million shares (USD 1.7 billion) bought back under the up to USD 5 billion share buyback announced in June 2018 and 13.8 million shares (USD 1.1 billion) to mitigate dilution related to participation plans of associates. In addition, 1.6 million shares (USD 0.2 billion) were repurchased from associates. In the same period, 15.0 million shares (for an equity value of USD 0.7 billion) were delivered as a result of options exercised and share deliveries related to participation plans of associates. Consequently, the total number of shares outstanding decreased by 19.4 million versus December 31, 2018. These treasury share transactions resulted in a decrease in equity of USD 2.3 billion and a net cash outflow of USD 2.4 billion (excluding Swiss Withholding Tax of USD 0.4bn on share buybacks to be paid in Q3 2019).

A total of 28.3 million shares have been purchased for a total of USD 2.5 billion under the up to USD 5 billion share buyback since its announcement in June 2018. This share buyback is expected to be completed by the end of 2019.

As of June 30, 2019, net debt increased by USD 1.7 billion to USD 17.9 billion versus December 31, 2018. The increase was mainly driven by the USD 6.6 billion annual dividend payment and the net cash outflow for treasury share transactions of USD 2.4 billion, partly offset by USD 5.5 billion free cash flow from continuing operations during the first half of 2019 and USD 2.9 billion net inflows related to the Alcon spin-off.

As of Q2 2019, the long-term credit rating for the company is A1 with Moody’s Investors Service and AA- with S&P Global Ratings.

2019 Outlook

Barring unforeseen events

New focused medicines company guidance
Excluding Alcon and the Sandoz US oral solids and dermatology business from both 2018 and 2019

Net sales revised upwards: expected to grow mid to high-single digit (cc).
From a divisional perspective, we expect net sales performance (cc) in 2019 to be as follows:
Innovative Medicines revised upwards: grow mid to high-single digit
Sandoz revised upwards: broadly in line to low-single digit growth
Core operating income revised upwards: expected to grow low double digit to mid-teens (cc).
The guidance above includes the forecast assumption that no Gilenya generics enter in 2019 in the US.

Foreign Exchange impact

If mid-July exchange rates prevail for the remainder of 2019, the currency impact for the year would be negative 3 percentage points on net sales and negative 4 percentage points on core operating income. The estimated impact of exchange rates on our results is provided monthly on our website.