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Heat Biologics Presents Interim Phase 2 Lung Cancer Data on HS-110 + Nivolumab at ASCO-SITC Clinical Immuno-Oncology Symposium

on February 28, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported updated interim results from its ongoing Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Heat Biologics, FEB 28, 2019, View Source [SID1234533839]). The results were presented today at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium by Daniel Morgensztern, M.D., Associate Professor of Medicine and Director of Thoracic Oncology, Washington University School of Medicine, and Lead Investigator in the trial. Data were presented on both Cohort A and Cohort B of the trial. Cohort A enrolls only previously treated patients who have never received a checkpoint inhibitor (CPI), while Cohort B enrolls patients who received a minimum of 4 months of treatment with a CPI as part of their prior therapy, but subsequently had documented progressive disease.

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"The treatment landscape for NSCLC has fundamentally changed as the number of patients who receive first line checkpoint inhibitor therapy is rapidly increasing," said COL(ret) George E Peoples, MD, FACS, Heat’s Chief Medical Advisor. "The preliminary data from our Cohort B is increasingly relevant and potentially exciting as it suggests that the addition of HS-110 to nivolumab may restore anti-tumor activity in patients whose disease has progressed after treatment with a CPI."

Jeff Hutchins, Ph.D., Chief Scientific and Operating Officer of Heat said, "The observed response rates and durability of disease stabilization support our mechanistic hypothesis that the broad, T-cell mediated immune response activated by HS-110 may improve patient survival when administered in combination with a CPI. The Cohort B data suggest that HS-110 may improve clinical outcomes for patients who have lost the benefit of treatment with a checkpoint inhibitor. We look forward to completing enrollment in this trial in Q2 and releasing additional results later this year as the data matures."

Highlights for both cohorts are presented below:

Cohort B (patients who progressed after ≥ 4 months of prior treatment with a checkpoint inhibitor)

Of first 20 patients enrolled in this cohort:

Partial response (PR) in 3 patients (15%) per RECIST 1.1 and 4 patients (20%) per investigator assessment

Disease control rate (DCR) of 55%

The 3 RECIST 1.1 PR patients had documented progression on CPI monotherapy immediately preceding study entry

Median progression free survival (mPFS) was 2.7 months (95% CI; 1.8 – 4.0 months)

Cohort A (patients who have never received a CPI prior to study entry)

Of 42 patients enrolled by the cutoff date:

PR in 9 patients (21%) per RECIST 1.1

DCR of 50%

Median overall survival not yet reached (60% still alive with a median follow-up of 14.4 months)

Responses and disease stabilization are durable and long-lasting

Subgroup analyses, predefined in the clinical protocol, were performed for levels of tumor-infiltrating lymphocytes (CD8+ TILs) present in tumors at baseline. A survival benefit [hazard ratio (HR) = 0.39] was observed in patients with levels CD8+ TIL <10% (i.e. "cold" tumors), a population that typically responds poorly to checkpoint inhibitors. The treatment benefit appeared to be independent of PD-L1 status (HR = 0.85)

Immune reactivity to HS-110 was measured via ELISPOT assay (high vs. low compared to median) on patient peripheral blood mononuclear cells obtained before and during treatment with a median overall survival benefit of 6.2 months in the high ELISPOT group

Overall survival was significantly higher in patients that experienced at least one dermal injection site reaction to HS-110 at any time during study treatment, supporting HS-110’s mechanism of action (HR = 0.15 [95% CI: 0.05-0.45], p=0.0001)

For both cohorts, treatment with HS-110 in combination with nivolumab was well tolerated, with no additional toxicities beyond those observed with single agent CPI therapy.

Importantly, data from Cohort B suggest that HS-110 in combination with nivolumab reduced tumor burden in patients whose disease progressed after treatment with a checkpoint inhibitor at any time prior to study entry. Additionally, the deepest responses were observed in three patients whose last treatment immediately preceding enrollment was checkpoint inhibitor monotherapy.

Also of interest is the data regarding overall survival (OS) in patients with low CD8+ TIL (tumor infiltrating lymphocytes) at baseline. Protocol-defined subgroup analysis of patients categorized as ‘high’ or low’ TIL, based on levels of CD8+ cells present in the stroma of their tumor tissue at baseline, demonstrate a survival advantage for the ‘low TIL’ group as compared to the ‘high TIL’ group (not reached vs. 13.8 months; HR = 0.39 [95% CI; 0.06-2.31]. These data are very encouraging as prior studies with nivolumab alone suggest that "cold" tumor patients with lower levels of baseline CD8+ TILs have lower response rates compared to "hot" tumor patients with high levels of CD8+ TILs1.

Trial results are summarized in the company’s updated corporate presentation, along with the official ASCO (Free ASCO Whitepaper)-SITC poster.

Trial Design

The Phase 2 trial is designed to evaluate the safety and efficacy of HS-110 combined with an immune checkpoint inhibitor for the treatment of advanced non-small cell lung cancer. Patients receive weekly HS-110 (1 x 107 cells) administered as 5 intradermal 0.1 mL injections for 18 weeks in combination with bi-weekly nivolumab 240 mg IV administered until confirmed disease progression or unacceptable toxicity, whichever occurs first. The primary endpoint is objective response rate (ORR); secondary endpoints include overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DOR). Exploratory endpoints include correlation of clinical outcomes to baseline CD8+ TILs, PD-L1 expression, peripheral blood tumor mutation burden and ELISPOT analysis.

For further details about the trial and the results presented at ASCO (Free ASCO Whitepaper)-SITC, refer to Heat Bio’s updated corporate presentation, which can be found on the Investors tab of the corporate website View Source

Intrexon Reports 2018 Fourth Quarter and Year End Financial Results

on February 28, 2019 Intrexon Corporation (NASDAQ: XON), a leader in the engineering and industrialization of biology to improve the quality of life and health of the planet, reported its fourth quarter and full year financial results for 2018 (Press release, Intrexon, FEB 28, 2019, View Source [SID1234533838]).

Recent Business Highlights:

Precigen, Inc., a wholly owned subsidiary of Intrexon, announced the US Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for PRGN-3006, an investigational drug for patients with relapsed or refractory acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS). PRGN-3006 is an autologous chimeric antigen receptor T-cell (CAR-T) therapeutic candidate utilizing Precigen’s transformative UltraCAR-T platform, which reduces manufacturing time to within two days following non-viral gene transfer;

Precigen announced the FDA cleared the IND application for PRGN-3005 UltraCAR-T, an investigational drug using CAR-T cells to treat advanced-stage platinum-resistant ovarian cancer patients and the first UltraCAR-T candidate targeting solid tumors to enter the clinic;

Following the previously reported reacquisition of oncology rights from Ziopharm in October 2018, Precigen and Intrexon entered into an agreement with Merck KGaA, Darmstadt, Germany, a leading science and technology company, and its wholly owned subsidiary Ares Trading, pursuant to which Intrexon assumed rights from Ares Trading under the existing agreement among Precigen, Ares Trading and Ziopharm relating to the development of CAR-T therapies. In addition to receiving 20,640,119 shares of Intrexon common stock, the agreement also included a further $25 million investment in the Company. In return, Merck KGaA, Darmstadt, Germany, received a $25 million convertible note, providing the option to receive either Precigen or Intrexon common stock;

Xogenex, a majority owned subsidiary of Intrexon, has completed an evaluation of three advanced heart failure patients who were administered INXN-4001, an investigational, non-viral, plasmid-based gene drug candidate designed to drive expression of three cardiac effector genes involved in heart failure, in a Phase 1 clinical trial. The data reflected the patients’ status six-months after being given the INXN-4001 and appears to indicate that the drug material and the delivery process were both well tolerated by the patients. Preliminary review of the data suggests improvements in several cardiac performance parameters;

Intrexon’s methane bioconversion platform is being employed to produce 2,3 BDO from natural gas and has achieved 80% of the goal for the first small-scale plant operations;

Detailed engineering design for Intrexon’s first-of-a-kind small-scale methane bioconversion facility to 2,3 BDO is currently being bid out, discussions with partners for sites are ongoing. The overall schedule is still consistent as the sites under consideration are brownfield which require less engineering time than the original greenfield concept;

Exemplar Genetics, a wholly owned subsidiary of Intrexon, announced the launch of a joint venture with the Mayo Clinic, which is focused on the development of a high-quality source of human liver cells or hepatocytes (HHCs);

Trans Ova Genetics, a wholly owned subsidiary of Intrexon, continues to expand and improve its herd genetics with two Jersey heifers ranking 2nd and 9th in the world and 15 bulls that rank at the top of the global Holstein bull population;

EnviroFlight, Intrexon’s joint venture with Darling Ingredients Inc., opened the very first commercial Black Soldier Fly (BSFL) facility, in Maysville, Kentucky in November 2018. The production plant has the ability to produce 900 tonnes/year of dried BSFL, and orders for product from the new facility account for one-third of the anticipated annual output;

Okanagan Specialty Fruits, a wholly owned subsidiary of Intrexon, harvested more than 2,100 bins of Arctic apples in their 2018 harvest, which are available at select retailers as fresh sliced apples and ApBitz dehydrated apple snacks, and is planning to plant up to 1,000,000 trees in the spring of 2019;

Intrexon entered into a strategic licensing agreement with Next Green Wave Holdings Inc. to utilize Intrexon’s Botticelli next generation plant propagation platform to enable rapid production of Next Green Wave’s proprietary cannabis cultivars for the California market;

Oxitec, Ltd., a wholly owned subsidiary of Intrexon, announced that it will be transitioning from its 1st generation self-limiting Friendly Aedes aegypti mosquito (OX513A) to a new Friendly Aedes mosquito (OX5034) that uses Oxitec’s 2nd generation technology, allowing the company to focus on advancing its entire mosquito and crop pest portfolios using this next-generation platform; and

Oxitec has secured two multi-year development agreements with a partner to develop solutions for pest problems beyond the mosquito, which have the potential for application in key markets globally.

Fourth Quarter 2018 Financial Highlights:

Total revenues of $43.2 million, a decrease of 44% from the fourth quarter of 2017;

Net loss of $340.5 million attributable to Intrexon, or $(2.59) per basic share, including non-cash charges of $311.0 million;

Adjusted EBITDA of $(27.2) million, or $(0.21) per basic share; and

Cash, cash equivalents, and short-term investments totaled $222.5 million and the value of common equity securities totaled $2.2 million at December 31, 2018.

Full Year 2018 Financial Highlights:

Total revenues of $160.6 million, a decrease of 31% from the full year ended December 31, 2017;

Net loss of $509.3 million attributable to Intrexon, or $(3.93) per basic share, including non-cash charges of $420.0 million; and

Adjusted EBITDA of $(102.5) million, or $(0.79) per basic share.

"With several of the most ambitious stated objectives at the time of our IPO now achieved, most notably with our work in UltraCAR-T and in natural gas upgrading, our team is more energized than ever to establish its tangible value in the world," commented Randal J. Kirk, Chairman and Chief Executive Officer of Intrexon. "We expect to achieve this initially through independent equitization and/or monetization events at Precigen and from our Methane Bioconversion Platform, while other business units of our company may also find higher values independently of our company."

Mr. Kirk concluded, "It has always been our purpose to be an enabler of enterprise that is built on engineered biology and not to create an industrial conglomerate. In this we have succeeded greatly so we look forward to seeing some of our bold enterprises making their marks in the world. We are confident in our prospects to achieve this and that we have adequate cash resources to fuel us to these realizations."

Fourth Quarter 2018 Financial Results Compared to Prior Year Period

Total revenues decreased $33.8 million, or 44%, from the quarter ended December 31, 2017. Collaboration and licensing revenues decreased $30.9 million from the quarter ended December 31, 2017 due to (i) the mutual termination in 2017 of the Company’s second exclusive channel collaboration (ECC) with Ziopharm for the treatment of graft-versus-host disease, (ii) a decrease in research and development services for certain of the Company’s ECCs as the Company redeployed certain resources towards supporting prospective new platforms and partnering opportunities and began to focus more on the further development of relationships and structures that will provide the Company with more control and ownership over the development process and commercialization path, including programs where the Company reacquired the previously licensed technology rights in 2018, and (iii) a decrease in research and development services performed by the Company for collaborators upon the transition of program execution to its collaborators. Product revenues decreased $2.8 million or 36% primarily due to lower milk prices which resulted in lower customer demand for cows and cloned products. Gross margin on products declined in the current period as a result of decreased sales. Gross margin on services improved in the current period as a result of pricing changes and an increase in the number of embryos produced per bovine in vitro fertilization cycle due to improved production results.

Research and development expenses increased $242.0 million, or 628%, and include $228.0 million of expenses related to in-process research and development reacquired from former collaborators. Selling, general and administrative (SG&A) expenses decreased $7.9 million, or 24%. This decrease was primarily due to lower compensation expenses due to adjustments to previously accrued compensation expenses for performance and retention incentives for SG&A employees in 2018. The Company recorded an impairment charge of $60.5 million in the fourth quarter of 2018 due to a change in the Company’s business strategy for commercializing the Oxitec technology targeting the Aedes aegypti mosquito.

Full Year 2018 Financial Results Compared to Prior Year Period

Total revenues decreased $70.4 million, or 31%, from the year ended December 31, 2017. Collaboration and licensing revenues decreased $68.7 million from the year ended December 31, 2017 primarily due to (i) the mutual termination in 2017 of the Company’s second ECC with Ziopharm for the treatment of graft-versus-host disease, (ii) a decrease in research and development services for certain of the Company’s ECCs as the Company redeployed certain resources towards supporting prospective new platforms and partnering opportunities and began to focus more on the further development of relationships and structures that provide the Company with more control and ownership over the development process and commercialization path, including programs where the Company reacquired the previously licensed technology rights in 2018, and (iii) a decrease in research and development services performed by the Company for collaborators upon the transition of program execution to its collaborators. Product revenues decreased $5.1 million or 15% primarily due to lower milk prices which in turn resulted in lower customer demand for live calves, cows previously used in production, and cloned products. Gross margin on products declined in the current period as a result of lower product sales and increased operating costs associated with new product offerings and cloned products. The increase in service revenues of $1.8 million, or 4%, as well as the gross margin thereon relates to pricing changes and an increase in the number of embryos produced per bovine in vitro fertilization cycle due to improved production results.

Research and development expenses increased $261.4 million, or 183%, and include $236.7 million of expenses related to in-process research and development reacquired from former collaborators. SG&A expenses decreased $8.3 million, or 6%, from the prior period. Legal and professional fees decreased $7.5 million primarily due to (i) decreased legal fees associated with ongoing litigation and (ii) decreased fees incurred for regulatory and other consultants. The Company recorded an impairment charge of $60.5 million in the fourth quarter of 2018 due to a change in the Company’s business strategy for commercializing the Oxitec technology targeting the Aedes aegypti mosquito.

Total other income (expense), net, decreased $41.5 million, or 185%. This decrease was primarily attributable to losses on the Company’s investment in Ziopharm preferred stock prior to returning this investment to Ziopharm in the fourth quarter of 2018, as well as an increase in interest expense related to the 3.5% convertible notes issued by the Company in the third quarter of 2018.

Based on Intrexon’s financial position, including its cash, cash equivalents and short-term investments of $224 million at December 31, 2018, in connection with issuing its financial statements Intrexon expects to include a conclusion in its Form 10-K that there is substantial doubt about its ability to continue as a going concern.

Conference Call and Webcast

The Company will host a conference call today Thursday, February 28th, at 5:30 PM ET to discuss the fourth quarter and full year 2018 financial results and provide a general business update. The conference call may be accessed by dialing 1-888-317-6003 (Domestic US), 1-866-284-3684 (Canada), and 1-412-317-6061 (International) and providing the number 4443860 to join the Intrexon Corporation Call. Participants may also access the live webcast through Intrexon’s website in the Investors section at View Source

Puma Biotechnology Reports Fourth Quarter and Full Year 2018 Financial Results

On February 28, 2019 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported financial results for the fourth quarter and year ended December 31, 2018 (Press release, Puma Biotechnology, FEB 28, 2019, View Source [SID1234533837]). Unless otherwise stated, all comparisons are for the fourth quarter and full year 2018, compared to the fourth quarter and full year 2017 .

Product revenue, net consists entirely of sales revenue from NERLYNX, Puma’s first commercial product. Net NERLYNX revenue in the fourth quarter of 2018 was $61.1 million, compared to net NERLYNX revenue of $20.1 million in the fourth quarter of 2017. Net NERLYNX revenue for the full year 2018 was $200.5 million, compared to net NERLYNX revenue of $26.2 million in 2017. Puma received approval from the U.S. Food and Drug Administration (FDA) for NERLYNX (neratinib) for the treatment of early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy on July 17, 2017, and the Company began shipment to wholesalers at the end of July 2017.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss of $30.7 million, or $0.80 per share, for the fourth quarter of 2018, compared to a net loss of $64.1 million, or $1.71 per share, for the fourth quarter of 2017. Net loss for the full year 2018 was $113.6 million, or $2.99 per share, compared to $292.0 million, or $7.85 per share, for the full year 2017.

Non-GAAP adjusted net loss was $12.2 million, or $0.32 per share, for the fourth quarter of 2018, compared to non-GAAP adjusted net loss of $38.6 million, or $1.03 per share, for the fourth quarter of 2017. Non-GAAP adjusted net loss for the full year 2018 was $26.7 million, or $0.70 per share, compared to non-GAAP adjusted net loss of $183.3 million, or $4.93 per share, for the full year 2017. Non-GAAP adjusted net loss excludes stock-based compensation expense. For a reconciliation of GAAP net loss to non-GAAP adjusted net loss and GAAP net loss per share to non-GAAP adjusted net loss per share, please see the financial tables at the end of this news release.

Net cash provided by operating activities for the fourth quarter of 2018 was $7.1 million, compared to net cash used in operating activities of $35.6 million for the fourth quarter of 2017. Net cash used in operating activities for the full year 2018 was $24.1 million, compared to $172.5 million for the full year 2017. At December 31, 2018, Puma had cash and cash equivalents of $108.4 million and marketable securities of $57.0 million, compared to cash and cash equivalents of $81.7 million at December 31, 2017.

"2018 was a strong year for Puma as we continued to grow NERLYNX sales, expanded our global presence and made progress in expanding the potential indications for the drug," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "This was highlighted by the European Commission granting marketing authorization in Europe, additional licensing agreements designed to provide access to NERLYNX in China, Latin America, Israel and Canada, and announcing data from the Phase III NALA trial, Phase II CONTROL trial, and Phase II SUMMIT trials."

Mr. Auerbach added, "During 2019, we anticipate the following key milestones for Puma: (i) meeting with the FDA and the European Medicines Agency to discuss data from the Phase III trial in third-line metastatic breast cancer patients in the first half of 2019; (ii) meeting with the FDA to discuss the clinical development and regulatory strategy for the SUMMIT trial in the first half of 2019; (iii) announcing regulatory decisions on neratinib for the extended adjuvant HER2-positive early stage breast cancer indication in countries outside of the United States and Europe in the first half of 2019; (iv) presenting data from the Phase III trial in third-line HER2-positive metastatic breast cancer treatment (NALA) in the first half of 2019; (v) reporting additional data from the Phase II CONTROL trial in the first half of 2019; and (vi) reporting Phase II data from the SUMMIT basket trial of neratinib in patients with HER2 mutations in the first half of 2019."

Revenue

Total revenue consists of product revenue, net from sales of NERLYNX, Puma’s first commercial product, and license revenue. For the fourth quarter ended December 31, 2018, total revenue was $71.1 million, of which $61.1 million was net NERLYNX revenue and $10.0 million was license revenue. For the year ended December 31, 2018, total revenue was $251.0 million, of which $200.5 million was net NERLYNX revenue and $50.5 million was license revenue received from Puma’s sub-licensees. This compares to total revenue of $27.7 million in 2017, of which $26.2 million was net NERLYNX revenue and $1.5 million was license revenue.

Operating Costs and Expenses

Total operating costs and expenses were $89.7 million for the fourth quarter of 2018, compared to $85.2 million for the fourth quarter of 2017. Total operating costs and expenses were $345.7 million for the full year 2018 compared to $320.1 million for the full year 2017.

Cost of Sales:

Cost of sales was $10.3 million for the fourth quarter and $34.6 million for the full year 2018, compared to $4.1 million for the fourth quarter and $5.6 million for the full year 2017.

Selling, General and Administrative Expenses:

Selling, general and administrative expenses were $41.0 million for the fourth quarter of 2018, compared to selling, general and administrative expenses of $30.9 million for the fourth quarter of 2017. Selling, general and administrative expenses for full year 2018 were $146.2 million, compared to $106.7 million for full year 2017, an increase of approximately $39.5 million. Increases in SG&A expenses for the full year 2018 primarily related to the hiring of a sales force and the commercial launch of NERLYNX, including approximately $18.9 million in payroll and related expenses, $8.2 million in travel and meetings, $6.0 million in professional fees, such as marketing, market access and analytics, $3.7 million in stock-based compensation and $2.6 million in other expenses, such as software and facilities, to support overall corporate growth.

Research and Development Expenses:

Research and development expenses were $38.4 million for the fourth quarter of 2018, compared to $50.2 million for the fourth quarter of 2017. Research and development expenses for the full year 2018 were $164.9 million, compared to $207.8 million for the full year 2017. The decrease of $42.9 million during the full year 2018 compared to the full year 2017 resulted primarily from decreases of approximately $25.5 million in stock-based compensation, $16.8 million in clinical trial expense, $2.6 million in consultant and contractor expense, partially offset by increases of approximately $2.0 million in R&D expenses primarily related to headcount additions in the medical affairs, quality assurance, regulatory affairs and pharmacovigilance.

Total Other Income (Expenses)

Total other expenses were $12.1 million for the fourth quarter of 2018, compared to total other expenses of $0.5 million for the fourth quarter of 2017. Total other expenses were $18.9 million for the year ended December 31, 2018, compared to total other income of $0.4 million for the year ended December 31, 2017. Other expense recorded in the fourth quarter of 2018 includes $9.0 million that represents an initial estimate of potential amounts that may be owed to class action participants as a result of the February 2019 jury verdict in a class action lawsuit, Hsu vs. Puma Biotechnology, Inc., et al.. The total amount of aggregate class-wide damages is uncertain and will be ascertained only after an extensive claims process and the exhaustion of any appeals. It is possible that the total damages will be higher than this estimate.

Conference Call

Puma will host a conference call to report its fourth quarter and full year 2018 financial results and provide an update on the Company’s business and outlook at 1:30 p.m. PST/4:30 p.m. EST on Thursday, February 28, 2019. The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international) at least 10 minutes prior to the start of the call and referencing the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on the Company’s website for 90 days.

Spectrum Pharmaceuticals Reports Fourth Quarter 2018 and Full Year 2018 Financial Results and Pipeline Update

On February 28, 2019 Spectrum Pharmaceuticals, Inc. (NASDAQ-GS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported financial results for the three-month period and year ended December 31, 2018 (Press release, Spectrum Pharmaceuticals, FEB 28, 2019, View Source [SID1234533836]).

"2018 was a very productive year for Spectrum in which our two promising pipeline products significantly progressed in clinical development," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "We begin 2019 with great momentum after meeting the enrollment target for the first cohort in our pivotal poziotinib study and submitting the BLA for ROLONTIS to the FDA at the end of 2018. In 2019, we are laser-focused on continuing to develop our two late-stage products, poziotinib and ROLONTIS, and looking for new opportunities that build upon these assets."

Pipeline update:

Poziotinib, an irreversible tyrosine kinase inhibitor targeting EGFR and HER2 mutations:

Enrollment in the EGFR, previously treated NSCLC cohort (cohort 1) in the ZENITH20 trial was completed; topline results are expected in Q4 2019.
Enrollment in the HER2, previously treated NSCLC cohort (cohort 2) in the ZENITH20 trial is expected to be completed in Q4 2019.
Initiation of pan-tumor and combination trials expected to be in H2 2019.
ROLONTIS (eflapegrastim), a novel long-acting GCSF:

Spectrum submitted the BLA with the FDA in late December 2018. Due to the government shutdown, the file was officially received on January 28, 2019.
Pipeline update continued:

Spectrum has begun launch readiness activities including inventory build and commercial preparedness.
Data from the Phase 3 study (RECOVER) was presented in a poster session at the San Antonio Breast Cancer Symposium in December 2018. The RECOVER study was the second pivotal trial to meet all primary and secondary endpoints and demonstrated comparable safety and tolerability profiles to pegfilgrastim.
2019 Guidance

Assuming the previously announced divestiture transaction closes in March, we expect 2019 SG&A costs to decrease by approximately 30 percent relative to 2018. We expect 2019 R&D costs to increase nominally as reduced spending on the legacy assets is offset by the increased spending on pre-commercial supply and tech transfer activities for ROLONTIS and poziotinib. With the increase of cash from the sale of our commercial assets, we expect our cash balance to be sufficient to fund operations for at least three years.

Three-Month Period Ended December 31, 2018 (All numbers are approximate)

GAAP Results

Total product sales were $28.0 million in the fourth quarter of 2018. Product sales in the fourth quarter included: FOLOTYN (pralatrexate injection) net sales of $12.2 million, EVOMELA (melphalan) for injection net sales of $7.5 million, BELEODAQ (belinostat) for injection net sales of $3.7 million, ZEVALIN (ibritumomab tiuxetan) net sales of $0.9 million, MARQIBO (vinCRIStine sulfate LIPOSOME injection) net sales of $2.3 million, KHAPZORY (levoleucovorin) net sales of $0.9 million, and FUSILEV (levoleucovorin) net sales of $0.4 million.

Spectrum recorded net loss of $49.2 million, or $0.47 per basic and diluted share in the three-month period ended December 31, 2018, compared to net loss of $28.6 million, or $0.29 per basic and diluted share in the comparable period in 2017. Total research and development expenses were $34.5 million in the quarter, as compared to $22.1 million in the same period in 2017. Selling, general and administrative expenses were $23.3 million in the quarter, compared to $29.2 million in the same period in 2017.

The company ended the quarter with cash, cash equivalents and marketable securities of $204 million.

Non-GAAP Results

Spectrum recorded non-GAAP net loss of $32.1 million, or $0.30 per basic and diluted share in the three-month period ended December 31, 2018, compared to non-GAAP net loss of $22.8 million, or $0.23 per basic and diluted share in the comparable period in 2017. Non-GAAP research and development expenses were $33.6 million, as compared to $21.3 million in the same period of 2017. Non-GAAP selling, general and administrative expenses were $19.9 million, as compared to $19.1 million in the same period in 2017.

Twelve-Month Period Ended December 31, 2018 (All numbers are approximate)

GAAP Results

Total product sales were $104.5 million for the twelve months ended December 31, 2018. Total product sales decreased 10.1% from $116.2 million in the same period of 2017.

Product sales in 2018 included: FOLOTYN (pralatrexate injection) net sales of $48.0 million, EVOMELA (melphalan) for injection net sales of $28.3 million, BELEODAQ (belinostat) for injection net sales of $12.3 million, ZEVALIN (ibritumomab tiuxetan) net sales of $7.0 million, MARQIBO (vinCRIStine sulfate LIPOSOME injection) net sales of $5.5 million, KHAPZORY (levoleucovorin) net sales of $0.9 million, and FUSILEV (levoleucovorin) net sales of $2.4 million. Spectrum recorded net loss of $120.0 million, or $1.16 per basic and diluted share in the twelve-month period ended December 31, 2018, compared to net loss of $91.2 million, or $1.07 per basic and diluted share in the comparable period in 2017. Total research and development expenses were $95.0 million for the year, as compared to $65.9 million in the same period in 2017. Selling, general and administrative expenses were $90.7 million for the year, compared to $84.3 million in the same period in 2017.

Non-GAAP Results

Spectrum recorded non-GAAP net loss of $86.8 million, or $0.84 per basic and diluted share in the twelve-month period ended December 31, 2018, compared to non-GAAP net loss of $52.1 million, or $0.61 per basic and diluted share in the comparable period in 2017. Non-GAAP research and development expenses were $91.0 million, as compared to $63.4 million in the same period of 2017. Non-GAAP selling, general and administrative expenses were $76.5 million, as compared to $65.4 million in the same period in 2017.

Conference Call

Thursday, February 28, 2019 @ 4:30 p.m. Eastern/1:30 p.m. Pacific

Domestic: (877) 837-3910, Conference ID# 2797623

International: (973) 796-5077, Conference ID# 2797623

This conference call will also be webcast. Listeners may access the webcast, which will be available on the investor relations page of Spectrum Pharmaceuticals’ website: View Source on February 28, 2019 at 4:30 p.m. Eastern/1:30 p.m. Pacific.

FDA Approves Herceptin Hylecta for Subcutaneous Injection in Certain HER2-Positive Breast Cancers

On February 28, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported the U.S. Food and Drug Administration (FDA) has approved Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) for subcutaneous (under the skin) injection for the treatment of certain people with HER2-positive early breast cancer (node-positive, or node-negative and ER/PR-negative or with one high-risk feature) in combination with chemotherapy and HER2-positive metastatic breast cancer in combination with paclitaxel or alone in people who have received one or more chemotherapy regimens for metastatic disease (Press release, Genentech, FEB 28, 2019, View Source [SID1234533835]). This new treatment includes the same monoclonal antibody as intravenous Herceptin (trastuzumab) in combination with recombinant human hyaluronidase PH20, an enzyme that helps to deliver trastuzumab under the skin. Herceptin Hylecta is a ready-to-use formulation that can be administered in two to five minutes, compared to 30 to 90 minutes for intravenous Herceptin.

"Over the past 20 years, Herceptin has significantly advanced treatment of HER2-positive breast cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "The approval of Herceptin Hylecta gives physicians and patients in the United States a new option to select treatment based on individual needs and preferences."

The FDA approval is based on results from three clinical studies in HER2-positive early breast cancer:

The Phase III HannaH study compared neoadjuvant (before surgery) and adjuvant (after surgery) Herceptin Hylecta to intravenous Herceptin, both in combination with chemotherapy. Subcutaneous administration of Herceptin Hylecta resulted in non-inferior levels of trastuzumab in the blood (pharmacokinetics) and non-inferior clinical efficacy (pathological complete response rate; pCR) compared to intravenous Herceptin.
The Phase III SafeHER study of adjuvant Herceptin Hylecta identified no new safety signals, with safety and tolerability consistent with the known safety profiles of intravenous Herceptin and Herceptin Hylecta.
The PrefHER patient preference study of adjuvant Herceptin Hylecta followed by intravenous Herceptin, or the reverse sequence, found the majority (86 percent) of people preferred Herceptin Hylecta over intravenous Herceptin.
The most common side effects in people receiving Herceptin Hylecta for early breast cancer were feeling tired, joint pain, diarrhea, injection site reaction, upper respiratory tract infection, rash, muscle pain, nausea, headache, swelling, flushing, fever, cough and pain in extremity.

For those who qualify, Genentech offers patient assistance programs for people prescribed Herceptin Hylecta by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit View Source for more information.

HannaH, SafeHER and PrefHER study results

HannaH
Herceptin Hylecta Intravenous Herceptin
pCR (absence of invasive cancer cells in the breast) 45.4% (118/260)
95% CI 39.2%-51.7%

40.7% (107/263)
95% CI 34.7%-46.9%

Mean level of trastuzumab in the blood (Ctrough) before dosing eighth cycle 78.7 mcg/mL 57.8 mcg/mL
Geometric mean ratio 1.3 (90% CI 1.2-1.4)
Most common adverse events (AEs; ≥10%)
Hair loss, nausea, administration-related reactions, feeling tired, decreased neutrophil count, diarrhea, rash, upper respiratory tract infection, vomiting, mouth blisters or sores, muscle pain, decreased appetite, constipation, radiation skin injury, damage to the nerves (numbness, tingling, pain in the hands/feet), joint pain, headache, flushing, fever, cough, low levels of red blood cells, difficulty breathing, incision site pain, low levels of white blood cells and, mucosal inflammation

SafeHER
Herceptin Hylecta
n=1,864

Safety No new safety signals for Herceptin Hylecta were identified. Safety and tolerability were consistent with the known safety profiles of intravenous Herceptin and Herceptin Hylecta.
Most common AEs (≥10%)
Administration-related reactions, feeling tired, diarrhea, injection site reaction, weakness, joint pain, rash, muscle pain, nausea, damage to the nerves (numbness, tingling, pain in the hands/feet), headache, swelling, flushing, fever, cough and pain in extremity

PrefHER
Herceptin Hylecta followed by intravenous Herceptin (n=121) or intravenous Herceptin followed by Herceptin Hylecta (n=119)
Patient preference 86% of people preferred Herceptin Hylecta, 13% preferred intravenous Herceptin, 1% had no preference
Reasons for preference The most common reason for preferring Herceptin Hylecta was time savings (179/231). The most common reason for preferring intravenous Herceptin was fewer local injection reactions.
About HER2-positive breast cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20 percent of breast cancers are HER2-positive based on the result of a diagnostic test.

About Herceptin Hylecta

Herceptin Hylecta (subcutaneous Herceptin) is a combination of trastuzumab and Halozyme Therapeutics’ Enhanze drug delivery technology. Trastuzumab is the same monoclonal antibody in intravenous Herceptin that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Herceptin is designed to block HER2 signaling that is believed to play a role in tumor growth and survival. Binding of Herceptin to HER2 may also signal the body’s immune system to destroy the cancer cells. Halozyme’s Enhanze technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan, a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.

Herceptin Hylecta Indication Statements

Adjuvant Breast Cancer

Herceptin Hylecta (trastuzumab and hyaluronidase-oysk) is approved for the treatment of adults with early stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2-positive) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin Hylecta can be used in several different ways:

As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as "AC→TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy).
Patients are selected for therapy based on an FDA-approved test for trastuzumab.

*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Herceptin Hylecta has two approved uses in adults with metastatic breast cancer:

Herceptin Hylecta in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of Human Epidermal growth factor Receptor 2-positive (HER2-positive) metastatic breast cancer.
Herceptin Hylecta alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.
Patients are selected for therapy based on an FDA-approved test for trastuzumab.

Important Safety Information

Possible serious side effects with Herceptin Hylecta

Not all people have serious side effects, but side effects with Herceptin Hylecta therapy are common.

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin Hylecta is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin Hylecta and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during, and after treatment with Herceptin Hylecta.

Patients should contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness.

SEVERE LUNG PROBLEMS, including:

Severe shortness of breath
Scarring of the lungs
Fluid in or around the lungs
Weakening of the valve between the heart and the lungs
Not enough oxygen in the body
Swelling of the lungs
A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

These signs usually happen within 24 hours after receiving Herceptin Hylecta.

A PATIENT SHOULD BE SURE TO CONTACT THEIR DOCTOR IF THEY:

ARE A WOMAN WHO COULD BECOME PREGNANT, OR MAY BE PREGNANT

Herceptin Hylecta may result in the death of an unborn baby or birth defects. Contraception should be used while receiving Herceptin Hylecta and for seven months after a patient’s last dose of Herceptin Hylecta. If a patient is or becomes pregnant while receiving Herceptin Hylecta or within seven months after their last dose of Herceptin Hylecta, the patient is encouraged to report Herceptin Hylecta exposure to Genentech at (888) 835-2555.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving intravenous trastuzumab plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Experience HYPERSENSITIVITY AND ADMINISTRATION-RELATED REACTIONS, which have been reported with Herceptin Hylecta. Serious and fatal reactions have been reported after treatment with intravenous trastuzumab products. A patient’s doctor will monitor them for signs of these reactions. Patients should contact their healthcare provider immediately if they experience any symptoms of hypersensitivity and administration-related reactions, including dizziness, nausea, chills, fever, vomiting, diarrhea, hives, swelling under the skin, breathing problems or chest pain.

SIDE EFFECTS SEEN MOST OFTEN

The most common side effects seen in treatment of adjuvant breast cancer with Herceptin Hylecta were tiredness, joint pain, diarrhea, injection site reaction, upper respiratory tract infection, rash, muscle pain, nausea, headache, swelling, flushing, fever, cough and pain in extremity.

The most common side effects seen in treatment of metastatic breast cancer (based on intravenous trastuzumab) are fever, chills, headache, infection, congestive heart failure, insomnia, cough and rash.

A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Herceptin Hylecta full Prescribing Information for additional Important Safety Information, including most serious side effects.

Herceptin Indication Statements

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2-positive) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as "AC→TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin) based therapy (a type of chemotherapy).
Patients are selected for therapy based on an FDA-approved test for Herceptin.

*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Herceptin has two approved uses in metastatic breast cancer:

Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of Human Epidermal growth factor Receptor 2-positive (HER2-positive) metastatic breast cancer.
Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.
Patients are selected for therapy based on an FDA-approved test for Herceptin.

Important Safety Information

Possible serious side effects with Herceptin

Not all people have serious side effects, but side effects with Herceptin therapy are common.

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during and after treatment with Herceptin.

INFUSION REACTIONS, including:

Fever and chills
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Pain (in some cases at tumor sites)
Headache
Dizziness
Shortness of breath
These signs usually happen within 24 hours after receiving Herceptin.

A patient should be sure to contact their doctor if they:

Are a woman who could become pregnant, or may be pregnant

Herceptin may result in the death of an unborn baby or birth defects. Contraception should be used while receiving Herceptin and for seven months after a patient’s last dose of Herceptin. If a patient is or becomes pregnant while receiving Herceptin or within seven months after their last dose of Herceptin, the patient should immediately report Herceptin exposure to Genentech at (888) 835-2555.

Have any signs of SEVERE LUNG PROBLEMS, including:

Severe shortness of breath
Fluid in or around the lungs
Weakening of the valve between the heart and the lungs
Not enough oxygen in the body
Swelling of the lungs
Scarring of the lungs
A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving Herceptin plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Side effects seen most often with Herceptin

Some patients receiving Herceptin for breast cancer had the following side effects:

Fever
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Infusion reactions
Diarrhea
Infections
Increased cough
Headache
Feeling tired
Shortness of breath
Rash
Low white and red blood cell counts
Muscle pain
A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Herceptin full Prescribing Information for additional Important Safety Information, including most serious side effects, at View Source

About Genentech in breast cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.