On July 16, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported financial results for the second quarter and six months ended June 30, 2019 (Press release, Seattle Genetics, JUL 16, 2019, View Source [SID1234537554]). The company also highlighted ADCETRIS (brentuximab vedotin) commercialization and clinical development accomplishments and progress with its late-stage clinical programs for cancer.

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"In the second quarter, we achieved record ADCETRIS net sales in the U.S. and Canada, reflecting growth in frontline CD30-expressing peripheral T-cell lymphomas as well as frontline advanced Hodgkin lymphoma," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "We are also making substantial progress with our late-stage programs, delivering on several key goals. The Biologics License Application for enfortumab vedotin was submitted to the FDA for patients with locally advanced or metastatic urothelial cancer, taking us another step closer to becoming a multi-product oncology company. Additionally, we expect to report topline data from the tucatinib pivotal trial, HER2CLIMB, in HER2-positive metastatic breast cancer later this year and from the tisotumab vedotin pivotal trial, innovaTV 204, in metastatic cervical cancer in the first half of 2020."

Program Highlights

ADCETRIS

Ex-U.S. Approvals for ADCETRIS in Frontline Hodgkin Lymphoma (HL): In May 2019, ADCETRIS in combination with AVD (Adriamycin, vinblastine and dacarbazine) was approved by Health Canada for patients with previously untreated stage IV HL. Also, in June 2019, Takeda received an additional approval for ADCETRIS in frontline HL that resulted in a $7.5 million milestone payment to Seattle Genetics.
Additional Analyses of ECHELON-1 and ECHELON-2 Trials Presented at 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting: A three-year update of the ECHELON-1 trial continued to show superior clinical activity of ADCETRIS in combination with AVD compared to ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) in frontline stage III and IV HL. Separately, analyses of clinical trials in T-cell lymphomas, including the ECHELON-2 trial, showed that responses were observed in patients across all levels of CD30 expression.
Enfortumab Vedotin

Enfortumab Vedotin Biologics License Application (BLA) Submitted to FDA: In July 2019, Seattle Genetics and Astellas Pharma, Inc. submitted a BLA to the U.S. Food and Drug Administration (FDA) for enfortumab vedotin to treat patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. The submission is based on positive results from the first cohort of the EV-201 clinical trial, which were recently presented in a late-breaking oral session at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting.
Broad Clinical Development Program Underway: Seattle Genetics and Astellas are evaluating enfortumab vedotin in several ongoing trials. These include a phase 3 randomized clinical trial (EV-301) that is intended to support global registrations. A phase 1 trial (EV-103) is also underway evaluating enfortumab vedotin in earlier lines of treatment for patients with locally advanced or metastatic urothelial cancer, including in combination with pembrolizumab and/or platinum chemotherapy in newly diagnosed patients as well as patients whose cancer progressed from earlier-stage disease. The company expects to report initial data from the EV-103 trial in 2019.
Tucatinib

Tucatinib HER2CLIMB Pivotal Trial Data Expected in 2019: The company previously announced enrollment of 480 patients in the HER2CLIMB pivotal trial of tucatinib in HER2-positive metastatic breast cancer to enable analysis of the primary endpoint of progression-free survival (PFS). Topline data are expected to be reported in 2019.
Tisotumab Vedotin

Tisotumab Vedotin innovaTV 204 Pivotal Trial Data Expected in 2020: Seattle Genetics and Genmab previously reported the completion of enrollment in the innovaTV 204 pivotal trial of tisotumab vedotin in patients with recurrent and/or metastatic cervical cancer who have relapsed or progressed after standard of care treatment. Topline data from the trial are expected in the first half of 2020.
Other Recent Activities

Collaborator ADC Progress: In June 2019, the FDA approved Polivy (polatuzumab vedotin-piiq) an antibody-drug conjugate (ADC) targeting CD79b that utilizes Seattle Genetics’ technology. Polivy was developed and will be commercialized by Genentech, a member of the Roche Group. As a result, Seattle Genetics will receive a $5.0 million milestone payment and is eligible to receive royalties on worldwide net sales.
Robin Taylor, Ph.D., Appointed Chief Commercial Officer: Dr. Taylor brings 18 years of biotechnology and pharmaceutical company experience in the commercialization of oncology drugs, including significant marketing, launch and global product strategy roles at both Genentech/Roche and AstraZeneca. He contributed to several leading global brands, including Tecentriq (atezolizumab), Alecensa (alectinib), Avastin (bevacizumab) and Herceptin (trastuzumab).
SECOND QUARTER AND SIX-MONTHS 2019 FINANCIAL RESULTS

Revenues: Total revenues in the second quarter and six-month periods ended June 30, 2019 increased to $218.4 million and $413.6 million, respectively, compared to $170.2 million and $310.8 million for the same periods in 2018. Revenues are comprised of the following three components:

Net Product Sales: ADCETRIS net sales for the U.S. and Canada in the second quarter were $159.0 million, a 30 percent increase over net sales of $122.4 million in the second quarter of 2018. ADCETRIS net sales for the U.S. and Canada were $294.0 million for the year-to-date in 2019, a 35 percent increase over net sales of $217.8 million for the same period in 2018.
Royalty Revenues: Royalty revenues in the second quarter were $23.3 million, compared to $20.6 million in the second quarter of 2018. Royalty revenues were $39.0 million for the year-to-date in 2019, compared to $36.2 million for the same period in 2018. Royalty revenues are primarily driven by sales of ADCETRIS outside the U.S. and Canada by Takeda, which increased for the periods in 2019 compared to the same periods in 2018.
Collaboration and License Agreement Revenues: Amounts earned under the company’s ADCETRIS and ADC collaborations increased to $36.1 million in the second quarter of 2019, compared to $27.2 million for the same period in 2018. Collaboration revenues were $80.7 million for the year-to-date in 2019, compared to $56.7 million for the same period in 2018. Collaboration revenues included the earned portion of $12.5 million and $42.5 million for milestones achieved in the second quarter of 2019 and first half of 2019, respectively. These milestones were based on Takeda’s additional approvals of ADCETRIS in frontline HL and Genentech’s FDA approval of Polivy.
Research and Development (R&D) Expenses: R&D expenses in the second quarter were $163.9 million, compared to $122.9 million in the second quarter of 2018. R&D expenses were $322.2 million for the year-to-date in 2019, compared to $275.4 million for the same period in 2018. The increases reflect additional investment in the company’s late-stage pipeline including enfortumab vedotin, tucatinib and tisotumab vedotin.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses in the second quarter were $82.3 million, compared to $58.3 million in the second quarter of 2018. SG&A expenses were $162.6 million for the year-to-date in 2019, compared to $124.5 million for the same period in 2018. The increases were primarily attributed to costs to support commercialization efforts related to frontline ADCETRIS indications, the company’s late-stage programs and higher infrastructure costs to support the company’s continued growth.

Non-cash, share-based compensation cost for the first six months of 2019 was $51.9 million, compared to $32.4 million for the same period in 2018.

Net Loss

Net loss for the second quarter of 2019 was $79.2 million, or $0.49 per diluted share, compared to net income of $76.3 million, or $0.47 per diluted share, for the second quarter of 2018. Net loss in the second quarter of 2019 included a net investment loss of $40.5 million primarily associated with Seattle Genetics’ common stock holdings, which are marked-to-market, compared to a net investment gain of $106.6 million in the second quarter of 2018. For the six months ended June 30, 2019, net loss was $92.6 million, or $0.57 per share, compared to a net loss of $35.4 million, or $0.23 per share, for the six months ended June 30, 2018. Net loss for the six months ended June 30, 2018 included an investment gain of $88.7 million.

Cash and Investments

As of June 30, 2019, cash and investments were $376.1 million. In addition, the company held stock investments, primarily in Immunomedics common stock, valued at $109.2 million.

2019 FINANCIAL OUTLOOK

The company’s 2019 financial guidance is detailed below, including updates to its expectations for collaboration revenues driven by recent milestones and SG&A expenses driven primarily by pre-commercialization activities for the potential launch of enfortumab vedotin in connection with the recent BLA submission.

Conference Call Details

Seattle Genetics’ management will host a conference call and webcast with supporting slides to discuss its second quarter 2019 financial results and provide an update on business activities. The event will be held today at 1:30 p.m. Pacific Time (PT); 4:30 p.m. Eastern Time (ET). The live event and supporting slides will be simultaneously webcast and available for replay from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 800-458-4121 (domestic) or 323-794-2093 (international). The conference ID is 3271918. A replay of the audio only will be available by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 3271918. The telephone replay will be available until 5:00 p.m. PT on July 19, 2019.

On July 16, 2019 Immunocore Limited, a leading T Cell Receptor (TCR) biotechnology company, reported the publication of "Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma" in a special issue on uveal melanoma in Cancers, an international, peer-reviewed monthly journal.1 Written by Dr. Bertil Damato, Dr. Richard Carvajal and experts at Immunocore, the paper provides an overview of the biology of uveal melanoma, the use of immunotherapy to treat metastatic disease and reviews tebentafusp, an investigational agent being studied for the treatment of metastatic uveal melanoma (Press release, Immunocore, JUL 16, 2019, View Source [SID1234537553]).

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Review Highlights1

Uveal melanoma is a rare and aggressive form of eye cancer that typically has a poor prognosis once it spreads beyond the eye.2 Nearly half of all patients diagnosed with uveal melanoma go on to develop metastatic disease. The median survival time after detection of metastases is around one year.2 Uveal melanomas have several characteristics that make them difficult to treat, including a low tumour mutational burden and low PD-L1 expression.1
Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. It is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect T cells to recognise and kill cancer cells.
Several studies with tebentafusp in both metastatic uveal melanoma and metastatic cutaneous melanoma are ongoing.
"With limited treatment options, the life expectancy of patients with metastatic uveal melanoma is dismal so that more effective therapies are urgently needed," said Dr. Damato, Senior Clinical Research Fellow at the University of Oxford. "We are encouraged by the work Immunocore is doing in the area of uveal melanoma."

– Ends –

About ImmTAC Molecules
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules that can potentially enable the immune system to recognise and kill cancerous cells. ImmTAC molecules are based on soluble TCRs engineered to recognise intracellular cancer antigens with ultra-high affinity and selectively kill cancer cells via an anti-CD3 immune-redirecting effector function. Based on the demonstrated mechanism of T cell infiltration into human tumours, the ImmTAC mechanism of action holds the potential to tackle solid "cold" low mutation rate tumours, the majority of tumours that historically have been difficult to treat.

On July 16, 2019 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported that its global biopharma partner Celgene Corporation has selected a lead therapeutic candidate in oncology for further development and exercised its option to a commercial license under the companies’ 2014 Azymetric collaboration and licensing agreement (Press release, Celgene, JUL 16, 2019, View Source [SID1234537552]). Zymeworks’ proprietary Azymetric technology platform enables the rapid development of bispecific and multifunctional therapeutics with broad potential for the treatment of cancer, inflammation, and infectious disease. Zymeworks will receive a US$7.5 million payment as a result of Celgene’s exercise of its option to a commercial license.

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"Celgene’s first selection of a lead bispecific antibody candidate using the Azymetric platform underscores their dedication to our partnership and the comprehensive utility of our industry-leading technologies," said Ali Tehrani, Ph.D., President and Chief Executive Officer at Zymeworks. "Celgene’s progress, alongside that of Lilly, Daiichi, and Merck, which we announced earlier this year, advances our goal of enabling innovative medicines for patients around the world."

Celgene is one of five global biopharmaceutical companies that has expanded their collaboration agreements with Zymeworks to increase the number of potential products commercialized based on the Azymetric platform. Under the terms of the original 2014 agreement, Zymeworks granted Celgene a license to research, develop, and commercialize up to eight bispecific antibodies, and in 2018, the companies increased the number of potential products to ten. For each of the up to ten products, Zymeworks is eligible to receive up to US$164 million comprised of a licensing fee and development and commercial milestones in addition to royalties on worldwide sales.

About the Azymetric Platform

The Azymetric platform enables the transformation of monospecific antibodies into bispecific antibodies, giving the antibodies the ability to simultaneously bind two different targets. Azymetric bispecific technology enables the development of multifunctional biotherapeutics that can block multiple signaling pathways, recruit immune cells to tumors, enhance receptor clustering degradation, and increase tumor-specific targeting. These features are intended to enhance efficacy while reducing toxicities and the potential for drug resistance. Azymetric bispecifics have been engineered to retain the desirable drug-like qualities of naturally occurring antibodies, including low immunogenicity, long half-life, and high stability. In addition, they are compatible with standard manufacturing processes with high yields and purity, potentially significantly reducing drug development costs and timelines.

On July 16, 2019 Vermillion, Inc. (Nasdaq: VRML), a bioanalytical-based women’s health company focused on gynecologic disease, reported publication of a paper entitled: "Clinical Performance Comparison of Two In-Vitro Diagnostic Multivariate Index Assays (IVDMIAs) for Presurgical Assessment for Ovarian Cancer Risk" in the journal Advanced Therapeutics (Shulman et al. Adv Ther. July 2019) (Press release, Vermillion, JUL 16, 2019, View Source [SID1234537551]). The study of 993 patients with 245 malignancies shows that Vermillion’s second generation multivariate index assay, Overa (MIA2G), had superior sensitivity to the current standards of care, Risk of Malignancy Algorithm (ROMA) and CA125, in detecting ovarian cancer, and the lowest false-negative rate in correctly characterizing ovarian malignancy risk.

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"These findings advance our ability to detect ovarian malignancy and provide clinicians with reliable tools to screen adnexal masses." said Lee Shulman, M.D., principal investigator and Anna Lapham Professor of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University. "The ability to better detect disease while reducing the number of missed cancer cases, is critical for improving outcomes for women with adnexal masses.

This is the first study published with respect to Overa since it received FDA approval. Key findings from the study include:

Overa exhibited a statistically significant higher sensitivity (91%; 95%CI, 86.8% – 94.0%) of malignancy detection than either ROMA (79.2%: 95%CI, 73.7% – 83.8%) or CA125 (71%; 95%CI, 65.0% – 76.30%), with the current ACOG guidance cutoff of 200 U/ml
Overa also outperformed CA125 in detection of combined early stage (I and II) cancer with a sensitivity of 90.5% (95%CI, 82.3% – 95.1%) for Overa and a sensitivity of 63.1% (95%CI, 52.4% – 72.6%) for CA125. Overa sensitivity also tended to outperform ROMA (76.2%; 95%CI, 66.1% – 84.0%) in detection of combined early stage (I and II) cancer.
Overa also tended to exhibit higher sensitivity than CA 125 and ROMA regardless of cancer type (epithelial, non-epithelial, low malignancy potential, metastatic, and non-metastatic)
Overa exhibited a significantly higher non-epithelial cancer sensitivity of 75% compared with 50.0% for ROMA, and 37.5% for CA125. This gap is significant as non-epithelial cancers are more prevalent in disparate populations.
Out of the 245 malignancies Overa exhibited the lowest rate of false negatives (8.9%) compared with CA125 (28.9%) or ROMA (20.8%)
As compared to CA125 and ROMA, Overa exhibited the highest sensitivity according to menopausal status. Overa also had identical sensitivity for pre- and post-menopause
"The findings from this study further establish that early stage risk assessment of ovarian cancer is possible with our OVA technology," said Valerie Palmieri, President and Chief Executive Officer of Vermillion, Inc. "The greatest barrier for women to obtain the proper treatment has been the lack of early detection tools, with the OVA technology the early stage risk assessment gap has finally been filled. Vermillion is committed to improving the pre-surgical pelvic mass assessment, so all stages, ages and ethnicities can access the right treatment at the right time."

Vermillion’s proprietary technologies, OVA1 and Overa, are FDA-cleared blood tests to evaluate cancer risk in women presenting with a pelvic mass, thus helping healthcare providers and women assess risk for malignancy prior to surgery.

On July 16, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:SGEN) reported submission of a Biologics License Application for accelerated approval to the U.S. Food and Drug Administration for the investigational agent enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting (Press release, Astellas, JUL 16, 2019, View Source [SID1234537550]).

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The submission is based on results from the first cohort of patients in the EV-201 pivotal phase 2 clinical trial that were presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June. Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a protein that is highly expressed in urothelial cancers.i

"There are limited treatment options for patients with advanced urothelial cancer, and we are encouraged by the results observed in the pivotal trial for enfortumab vedotin," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

"There is an urgent need for new therapies for patients with advanced urothelial cancer, and we look forward to working with our partner Astellas and the FDA on the review of this application," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

Based on preliminary results from a phase 1 trial (EV-101), the FDA granted enfortumab vedotin Breakthrough Therapy designation for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following checkpoint inhibitor therapy.

A global, randomized phase 3 confirmatory clinical trial (EV-301) is ongoing and is intended to support global registrations. Another ongoing trial, EV-103, is evaluating enfortumab vedotin in earlier lines of treatment for patients with locally advanced or metastatic urothelial cancer, including in combination with pembrolizumab and/or platinum chemotherapy in newly diagnosed patients as well as patients whose cancer progressed from earlier-stage disease.