On July 16, 2019 Cytori Therapeutics, Inc. (Nasdaq: CYTX) (the "company") reported a new direction and identity (Press release, Cytori Therapeutics, JUL 16, 2019, View Source [SID1234572285]).

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Since the beginning of 2019, the company has successfully evaluated and transformed its pipeline to place a stronger emphasis on product candidates that can maximize returns for shareholders and make a clinically meaningful impact for patients. Plus Therapeutics, Inc. plans to create and realize this value by developing drugs for niche and orphan markets, initially in oncology, that address significant unmet or substantially underserved medical needs and that represent global revenue opportunities estimated to be $250 million or more. We intend to focus our development activities in ways that can leverage the U.S. FDA’s accelerated regulatory pathways and enable the company to apply its in-house expertise in nanoparticle drug design, complex formulation, and drug manufacturing and scale-up.

"Our core development concept will be to combine known active pharmaceutical ingredients, or drugs, with new delivery approaches and/or formulations, resulting in innovative therapies with improved safety, efficacy, and/or convenience," said Marc H. Hedrick MD, President and CEO.

The company’s initial development focus will be on DocePLUS (formerly ATI-1123) — a complex, injectable, patented, albumin-stabilized pegylated liposomal docetaxel — for which a U.S. Phase 1 clinical trial has been completed and published. The company has previously announced that it has received feedback from the U.S. FDA that a 505(b)(2) new drug application appears to be an acceptable regulatory approach for DocePLUS. Plus Therapeutics intends to submit a Phase 2 clinical trial protocol in Small Cell Lung Cancer patients with platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy to the U.S. FDA in the second half of 2019.

Coinciding with this new focus on DocePLUS, the company has determined that DoxoPLUS (formerly ATI-0918) –- a generic pegylated liposomal doxorubicin — no longer satisfies the aforementioned development and revenue criteria. As a result, we have elected to focus on divesting DoxoPLUS and are currently presenting this opportunity to external parties.

To complement and reinforce the new company direction, a new company brand will be established. We have created, designed, and launched a new company visual identity, mission, vision, values, website, and social media sites based on the brand promise of ‘Delivering More For Patients’.

"We took a holistic approach to branding the company under the new Plus Therapeutics name," said Russ Havranek, Vice President, Marketing and Portfolio Management. "We believe that Plus Therapeutics will clearly align, drive, and navigate the business forward, ultimately helping patients who are battling cancer and other life-threatening diseases."

The company has reserved a new stock symbol, PSTV, and plans to submit notice of the company name change to the Nasdaq Stock Exchange. We expect to trade under the new symbol within the next few weeks. Until then, the company intends to continue to trade on Nasdaq under its current stock symbol, CYTX.

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 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a clinical-stage biopharmaceutical company focused on the development of novel therapeutics for the treatment of rare diseases, and Abbisko Therapeutics, a company with an extensive pipeline of targeted therapeutics with first-in-class or best-in-class potential, reported they have entered into an agreement to develop and commercialize X4’s product candidate, mavorixafor, in combination with checkpoint inhibitors or other agents in Greater China for oncology indications. Mavorixafor is a potentially first-in-class, once-daily, oral, small molecule antagonist of chemokine receptor CXCR4 (Press release, Abbisko Therapeutics, JUL 16, 2019, View Source;article_id=104 [SID1234556282]).

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This agreement provides Abbisko with the exclusive rights in China, Taiwan, Hong Kong and Macau to develop and commercialize maxorixafor in combination with checkpoint inhibitors or other agents in oncology indications – including pancreatic cancer, ovarian cancer and triple negative breast cancer, which will be explored initially. X4 retains full rest-of-world rights to develop and commercialize mavorixafor outside of Greater China for all indications, and the ability to utilize any data generated pursuant to the Abbisko collaboration for rest-of-world development.

"We are pleased to enter into this strategic partnership with the experienced team at Abbisko. This collaboration enables us to leverage Abbisko’s research and development expertise to explore mavorixafor’s potential benefit in advanced cancer patients and to potentially capture value from the growing oncology markets in Greater China, while enabling X4 to maintain its focus on the company’s ongoing rare disease programs," commented Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. "Abbisko’s top-notch investor syndicate, strong leadership with global oncology R&D experience, and broad healthcare network in Greater China provide a complementary opportunity to expand mavorixafor’s potential for patients into solid tumor oncology indications, which represent areas of significant unmet need."

"Mavorixafor has demonstrated proof of concept and a favorable safety profile in a Phase 2 trial in patients with WHIM syndrome, which is caused by compromised immune cell trafficking. We look forward to further realizing mavorixafor’s potential in broad oncology indications in combination with immune checkpoint inhibitors and other therapies, for the benefit of patients with significant unmet medical needs," said Dr. Yaochang Xu, Chief Executive Officer of Abbisko Therapeutics. "Targeting CXCR4 has strong mechanistic rationales in oncology and we believe mavorixafor will bring transformative value to Abbisko’s portfolio with clear synergies with our internal pipeline programs."

About Mavorixafor

X4 Pharmaceutical’s lead product candidate, mavorixafor (X4P-001), is a potentially first-in-class, once-daily, oral inhibitor of CXCR4, currently in Phase 3 development for the treatment of WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. Mavorixafor has demonstrated proof of concept in WHIM in a Phase 2 trial, including clinically meaningful increases in neutrophil and lymphocyte biomarker counts, as well as a trend of reduction in infection rates and wart burden, and a favorable safety profile. Mavorixafor was designated orphan drug status by the U.S. Food and Drug Administration in 2018 for the treatment of WHIM and is also in development for Severe Congenital Neutropenia (SCN), Waldenström’s macroglobulinemia (WM), and clear cell renal cell carcinoma (ccRCC).

On July 16, 2019 Cyclica, a Toronto-based biotechnology company leveraging AI and computational biophysics for drug discovery, and Professor Igor Stagljar from the Donnelly Centre for Cellular and Biomolecular Research, Department of Biochemistry & Department of Molecular Genetics at the University of Toronto, reported a collaboration to optimize lead compounds and de novo design of novel compounds in an effort to advance precision medicine with the next-generation EGFR-inhibitors in non-small cell lung cancer (NSCLC) (Press release, Cyclica, JUL 16, 2019, View Source [SID1234537555]). The Stagljar Lab is located in the Donnelly Centre, a cutting-edge, interdisciplinary research institute in the heart of Toronto’s research district.

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NSCLC makes up approximately 85% of lung cancers. Evolved drug resistance has been a key challenge for treating NSCLC due to EGFR mutations, which are present in roughly 17% of people with lung cancer in the United States. The prevalence of these mutations increase to 50% in people of Eastern Asian descent, and are more common in women than men. Additional research in treating NSCLC is critical to developing effective precision medicines that can target the evolving nature of this disease.

MatchMaker, Cyclica’s proprietary deep learning protein-ligand binding technology, will be used to batch deconvolute a shortlist of shared targets among a group of promising lead compounds identified at the Stagljar Lab using their proprietary MaMTH-Drug Screening (MaMTH-DS) assay to drive new mechanistic insights of such a disease. Ligand Design, Cyclica’s multi-targeted and multi-objective drug design platform, will then create structural variants of the existing lead compounds, and computationally design novel compounds that have the preferred polypharmacological, pharmacokinetic, and physicochemical properties. Recently, Nature Medicine online published an article featuring Cyclica’s drug discovery platforms, and highlighted the value of designing multi-targeted drugs for oncology. The Stagljar Lab will synthesize selected the novel compounds, and conduct downstream validation through its proprietary set of assays for further research and commercialization opportunities. All IP generated from this project related to the compounds will be shared equally by Cyclica and the University of Toronto.

"We are thrilled to be working with the world class Stagljar Lab to leverage our drug discovery platform to progress our shared interests in creating novel advanced lead compounds for non-small cell lung cancer," says Naheed Kurji, President & CEO, Cyclica. "This project is an example of the growing integration between science and industry focused on commercialization, and a testament to the hyper innovative work being done in our own backyard at the University of Toronto."

"We are extremely pleased to be working with Cyclica since our collaboration represents a unique approach that unites two completely novel and complementary approaches, Cyclica’s artificial intelligence MatchMaker and our MaMTH-DS live-cell drug discovery assay, for the rapid identification and validation of novel EGFR inhibitors in NSCLC. I’m positive that our joint efforts will accelerate our ability to build novel EGFR inhibitors with these cutting-edge technologies and will thus speed up their implementation in the clinics," says Dr. Igor Stagljar, University of Toronto.

Cyclica is a Toronto-based, globally recognized biotechnology company that leverages AI and computational biophysics to reshape drug discovery. Cyclica provides the pharmaceutical industry with Ligand Express and Ligand Design, an integrated, holistic, and end-to-end enabling platform focused on polypharmacology. Ligand Design and Ligand Express augment how scientists design advanced lead like molecules that minimize off-target effects, and gain insights into structural pharmacogenomics. By doing more with artificial intelligence, Cyclica aims to revolutionize a system troubled with attrition and costly failures, accelerate the drug discovery process, and develop medicines with greater precision.

The Stagljar Lab at the University of Toronto is focused on protein-protein interactions (PPIs), with a particular interest in disease progression due to altered signalling pathways. They examine how proteins involved in these signalling pathways interact with each other, and try to understand how impaired PPIs lead to numerous human diseases such as lung cancer, pancreatic cancer, breast cancer, brain cancer and aging. In close collaboration with medicinal chemists and clinical investigators, the Stagljar lab investigates the molecular mechanisms behind challenging, unexplained observations on drugs and on pathological events.

The Donnelly Centre for Cellular and Biomolecular Research is an interdisciplinary research institute at the University of Toronto in which scientists make fundamental discoveries in biology to improve health. Founded in 2005, the Centre is globally recognized as a leading biomedical research hub thanks to our researchers’ landmark discoveries in genetics, stem cell biology and the molecular basis of disease, as well as state-of-the-art tools in large-scale data analysis. As well as making discoveries, our researchers also strive to translate their findings into tangible advances in medicine to help patients.

On July 15, 2019 Advaxis, Inc. (NASDAQ: ADXS), a clinical-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported new immune data from its ongoing ADXS-NEO Phase 1 clinical trial that further support the clinical potential for the company’s platform in neoantigen-directed immunotherapies (Press release, Advaxis, JUL 15, 2019, View Source [SID1234537523]).

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ADXS-NEO is a personalized immunotherapy that is designed to help a patient’s immune system recognize and respond to mutation-derived tumor antigens, or neoantigens, that are unique to his or her tumor. ADXS-NEO is designed to express tLLO fused to up to 40 patient-specific neoantigens arranged sequentially as beads-on-a-string. As a live attenuated bacterial vector, ADXS-NEO can be rapidly taken up by antigen presenting cells, which recognize it as foreign and present the tLLO-NEO fusion proteins to T cells by the major histocompatibility complex class I and II pathways.

ADXS-NEO is being evaluated in an open-label, dose-escalation, multicenter Phase 1 clinical trial in the United States. Part A of the study is open to patients with metastatic non-small cell lung cancer (NSCLC), metastatic microsatellite stable colorectal cancer (MSS-CRC) and metastatic squamous cell carcinoma of the head and neck (SCCHN) who will receive ADXS-NEO as monotherapy. Part B of the study, anticipated to begin later this year, will be open to NSCLC patients as well as patients with melanoma SCCHN and bladder cancer and, for this part, ADXS-NEO will be administered in combination with a checkpoint inhibitor.

The new data were derived from deconvolution of neoantigen pools using single peptides and in vitro stimulation ELISpot assays (minimal CD8+ peptides). This has now been completed for the first two patients enrolled in this study, one with NSCLC and one with MSS-CRC. Highlights of the new post-vaccination data with ADXS-NEO are as follows:

CD8+ T cells were generated against 90% of the 40 neoantigen targets contained in the drug construct for the MSS-CRC patient (the NSCLC patient did not have 40 neoantigen targets and there were certain other issues with this patient’s sample that, together, made it unsuitable for inclusion in this "hit rate" analysis). This is consistent with Advaxis’ previously reported data from its preclinical studies as well as from clinical studies using pooled neoantigen peptides which were presented at the American Association of Cancer Research Annual Meeting last year and earlier this year, respectively. This is the highest "hit rate" publicly reported to-date in the neoantigen field. This high "hit rate", along with the rapid immune responses seen and antigen spreading, lay the foundation for the ADSX-NEO platform to be best-in-class for personalized, neoantigen-directed immunotherapies.

CD8+ T cells were also generated against the hotspot mutations found within each of the two patients’ tumors (i.e., EGFRL858R in the NSCLC patient and KRAS G12A in the MSS-CRC patient). This is important for the ADXS-NEO program as Advaxis believes a number of patient tumors likely will present with hotspot mutations, and generating or maintaining CD8+ T cell activity against these targets may increase the potential for killing cancer cells. All of the first four patients in this Phase 1 trial had a hotspot mutation. This is also relevant for the company’s ADXS-HOT program in that this is the first time Advaxis has observed the ability to generate or maintain specific CD8+ T cell activity against hotspot mutations. Hotspot mutations are important targets contained within the numerous drug constructs within the ADXS-HOT program and the specific hotspot mutations in these two patients, EGFRL858R and KRAS G12A, are included in the company’s ADXS-503 (HOT Lung) and ADXS-508 (HOT Colorectal) drug constructs, respectively.

Antigen spreading was confirmed in the MSS-CRC patient showing specific CD8+ T cells against neoepitopes that were not contained in the drug construct prepared for this patient (the NSCLC patient’s sample was not re-tested for antigen spreading). Thus, Advaxis believes ADXS-NEO may be able to induce a specific immune response against neoantigen-bearing tumor cells with the resultant cell death releasing secondary (nontargeted) tumor antigens. These secondary antigens can then prime subsequent immune responses (antigen spread) that are thought to be responsible for the improved clinical outcomes documented with other immunotherapies. Of note, antigen spreading has also been induced with other Lm constructs such as ADXS-HPV and ADXS-PSA in cervical and prostate cancer patients, respectively.

To date, dosing of ADXS-NEO at 1×108 colony forming units (CFU) has been well-tolerated in two patients. ADXS-NEO dosed at 1×109 CFU was beyond the maximum tolerated dose with reversible Grade 3 hypoxia (n=2) and Grade 3 hypotension (n=1) dose-limiting toxicities.

"This preliminary dataset of the deconvolution assays shows the generation of specific CD8+ T cell response in one MSS-CRC patient against 90% of the neoantigens in that patient’s personalized Lm construct together with antigen spreading, both of which we believe are critical for potential clinical benefit. These encouraging results are consistent with data from our previous preclinical and ELISpot-pooled clinical studies, and we look forward to presenting data from all patients in the monotherapy arm later in the year," said Andres Gutierrez, M.D., Ph.D., Chief Medical Officer of Advaxis. "In addition, we are gaining valuable insight from our ADXS-NEO platform to help advance our ADSX-HOT drug constructs, as for the first time we observed the ability to generate specific CD8+ T cell activity against hotspot mutations in the clinic. We continue to enroll patients in this Phase 1 study for ADXS-NEO and look forward to starting Part B with ADXS-NEO in combination with a checkpoint inhibitor later this year."