On October 19, 2018 Incyte (NASDAQ:INCY) reported Phase 2 preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Incyte, OCT 19, 2018, View Source [SID1234530093]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0 percent (95% CI: 50.6-87.9) in treatment-naive patients and 39.1 percent (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed.

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Results of the Novartis-sponsored Phase 2 study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (October 19, 2018 at 4:45 p.m. CEST / 10:45 a.m. EDT, Abstract LBA52).1

"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, M.D., University Hospital Cologne, Germany.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year.2 Approximately 3-4 percent of all patients with NSCLC have an identified MET mutation.3 Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation.4

"We are very pleased to announce these promising, preliminary results for capmatinib, another investigational medicine invented at Incyte that has the potential to be the first MET-selective targeted agent approved by the FDA," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We are encouraged by the results of this study and the potential for capmatinib to help patients with advanced MET mutated NSCLC, who face a poor prognosis and represent a clear unmet medical need."

About GEOMETRY mono-1

The GEOMETRY mono-1 trial is a multicenter, open-label, Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0 percent (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1 percent (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response.1,6

The most common treatment-related AEs included peripheral edema, nausea, vomiting and increased blood creatinine levels. Of patients treated with capmatinib, 83.8 percent experienced an AE, with 33.1 percent having grade 3/4 AEs.1,6

About Capmatinib

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor invented at Incyte that was licensed to Novartis in 2009. Under the Agreement, Incyte granted Novartis exclusive development and commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications. Novartis has stated that it expects to submit a new drug application to the U.S. Food and Drug Administration for capmatinib as a treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring MET amplification and/or mutations in 2019. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 percent and 14 percent on global sales by Novartis.

On October 19, 2018 ArQule, Inc. (Nasdaq:ARQL) reported the presentation of preliminary clinical data on miransertib (ARQ 092) in three poster presentations at the American Society of Human Genetics (ASHG) 2018 Annual Meeting held from October 16 to 20, 2018 in San Diego (Press release, ArQule, OCT 19, 2018, View Source [SID1234529975]). The data presented relate to patients affected by either Proteus syndrome or PROS who have been receiving miransertib as part of a clinical trial or in a compassionate use setting.

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Two presentations feature data from two patients treated as part of ArQule’s named patient/compassionate use program. Presentation highlights include:

1.Personalized medicine in rare diseases and cancer: A case report of a lasting response in a young teenage patient with Proteus syndrome and secondary ovarian cancer

Treatment for the Proteus syndrome patient with concomitant relapsed ovarian cancer was administered at a dose level of 100mg and was well tolerated for over 19 months, resulting in a clinically significant/durable partial response of tumor and improvement of Proteus syndrome symptoms including improved mobility/bone changes
2.Severe PI3Kinase overgrowth syndrome treated with the AKT inhibitor miransertib

Treatment for the PROS patient was well tolerated for over 25 months resulting in clinical stabilization and radiological improvement of disease
"Our understanding of the potential for miransertib to target and treat these rare and devastating diseases that arise due to genetic alterations of the PI3K/AKT pathway has grown significantly since we partnered with The National Human Genome Research Institute in 2015 to conduct the first clinical trial in Proteus syndrome," said Brian Schwartz, M.D., Chief Medical Officer of ArQule. "The data we are presenting at ASH (Free ASH Whitepaper)G continues to highlight the promise of ArQule’s precision medicine approach for both rare diseases and oncology. We remain deeply committed to advancing miransertib for rare PI3K/AKT pathway overgrowth diseases as rapidly as possible, as there are currently no approved therapeutics for these patients."

A third presentation features data from patients treated as part of ArQule’s ongoing Phase 1/2, open label study of miransertib for the treatment of PROS. Study objectives include the evaluation of dosing schedule, safety, PK profile and preliminary efficacy of miransertib. Presentation highlights include:

3.An open-label, phase 1/2 study of miransertib (ARQ 092), an oral pan-AKT inhibitor, in patients (pts) with PIK3CA-related Overgrowth Spectrum (PROS): Preliminary results

Preliminary evidence of clinical efficacy was demonstrated by improvements in disease related symptoms and objective radiologic and photographic measures
Miransertib was well tolerated with a demonstrated manageable toxicity profile in patients as young as two years old
The recommended dose of miransertib, defined as 15 mg/m2 QD, with potential dose escalation to 25 mg/m2 QD, provided appropriate inhibition of the activated PIK3CA pathway for long-term use without inhibition of growth in normal healthy cells
Peter Lawrence, President and Chief Operating Officer of ArQule said: "This initial presentation of clinical data from our Phase 1/2 study in PROS lays the foundation for potentially expanding the miransertib rare disease program beyond Proteus syndrome, for which the drug already has received Rare Pediatric Disease and Fast Track Designation. We look forward to continuing our productive discussions with regulators to define a pivotal trial design and rapidly advance miransertib."

All posters presented by ArQule at the ASH (Free ASH Whitepaper)G 2018 Annual Meeting are available on the company’s website at View Source

About Miransertib
Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers; however, there are currently no approved inhibitors of AKT. AKT inhibitors, either as single agent or combination therapy, show significant promise in molecularly defined patient populations. Miransertib is currently in a Phase 1/2 company-sponsored study for PIK3CA-Related Overgrowth Spectrum (PROS), a Phase 1 study for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH/NHGRI), and a Phase 1b study in combination with the hormonal therapy, anastrozole, in patients with advanced endometrial cancer with AKT and PI3K mutations. Miransertib has been granted Rare Pediatric Disease Designation and Fast Track Designation by the U.S. Food and Drug Administration (FDA), as well as Orphan Designation by the FDA and European Medicines Agency in the rare overgrowth disease, Proteus syndrome.

About PROS
PROS is a term used to refer to a spectrum of rare diseases identified by somatic mutations in the PIK3CA gene, that result in excess growth in certain areas of the body. While the individual diseases that fall within the overgrowth spectrum have similar symptoms, each disease is defined by unique clinical characteristics. The implementation of genetic sequencing has led to the identification of the underlying genetic mutations that drive these overgrowth disorders, allowing for the development of medicines that target the specific causes of disease.

About Proteus Syndrome
Proteus syndrome is an ultra-rare condition characterized by the aberrant overgrowth of multiple tissues of the body. Patients with Proteus syndrome experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body. Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first 10 years of life. The worldwide incidence is believed to be approximately one in a million. There are currently no approved medicinal treatments for Proteus syndrome, leaving patients with minimal treatment options to manage the disease and a mortality of 25% by age 22.

On October 19, 2018 SELLAS Life Sciences Group Inc., (Nasdaq: SLS) (SELLAS or the Company), a clinical-stage biopharmaceutical company focused on novel cancer immunotherapies for a broad range of cancer indications, reported that the independent Data Safety Monitoring Board (DSMB) unanimously concluded that the final data from the Phase 2b study of trastuzumab (TZ, Herceptin) +/- nelipepimut-S (NPS, NeuVax) in HER2 1+/2+ breast cancer patients confirms the previously announced findings from the interim analysis of this study (Press release, Sellas Life Sciences, OCT 19, 2018, View Source [SID1234529976]). The DSMB concluded that there was an incremental improvement in the outcomes and statistics with a longer median follow-up (more than 7 months; 26.1 months at final vs. 18.8 months at interim analysis). The final analysis showed no new safety signals and continued to show no difference in cardiotoxicity between TZ + NPS compared to TZ alone. Finally, the DSMB confirmed that the final analysis continues to identify patients with triple negative breast cancer (TNBC) as the key target patient population for development of the NPS + TZ combination in the adjuvant setting in early-stage HER2 1+/2+ breast cancer patients.

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On March 28, 2018, based on a pre-specified interim analysis and the positive TNBC results, the DSMB had recommended to expeditiously seek regulatory guidance by the U.S. Food and Drug Administration (FDA) for further development of the combination of NPS + TZ in TNBC, a population with large unmet medical need.

SELLAS will host a conference call at 8:00 a.m. ET on October 22, 2018, following the oral presentation at the ESMO (Free ESMO Whitepaper) 2018 Annual Meeting of the interim and updated final clinical data from its Phase 2b trial of the combination of trastuzumab (Herceptin) +/- nelipepimut-S (NPS, NeuVax) targeting HER2 low-expressing breast cancer patient cohorts. Management and invited Key Opinion Leaders, Dr. Elizabeth Mittendorf, MD, PhD and Dr. George Peoples, MD, FACS, will participate in the conference call.

Conference Call Details for Monday, October 22, 2018 at 8:00 a.m. ET:

To participate in the conference call, please dial (866) 416-7995 (domestic) or +1 (409) 217-8225 (international) and refer to conference ID 5571389. A live webcast of the call can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.sellaslifesciences.com.

An archived webcast recording will be available on the SELLAS website beginning approximately two hours after the call.

Details for the ESMO (Free ESMO Whitepaper) presentation are as follows:
Title:Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipepimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients
Date and Time: 22 October, 2018; 11:54 am Central European Time (5:54 am ET)
Location: Hall A2 – Room 18; Messe Munich Congress Venue, Munich, Germany

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

About ESMO (Free ESMO Whitepaper)

The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) is Europe’s leading non-profit medical oncology organization. ESMO (Free ESMO Whitepaper) is a membership-based society, comprising of 500 expert committee members and 18,000 oncology professionals. ESMO (Free ESMO Whitepaper) organizes a large number of meetings to provide its members and the community with the resources they need and also plays a major role in public policy and European affairs. The ESMO (Free ESMO Whitepaper) 2018 Annual Meeting represents a multi-professional platform for oncology education and exchange, and for immense international visibility for scientific research, and will be held under the tagline "Securing access to optimal cancer care."

A recent analysis from 1stOncology/BioSeeker reveals the direction of commercial drug development emerging from the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 congress, featuring more than 2000 abstracts detailing the latest ground-breaking science/clinical development in oncology.

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While this analysis tells you all from which immunotherapies are dominating at E.S.M.O to development of novel targets, never previously pursued in oncology, the center stage for the “Commercial Interest at E.S.M.O Annual Meeting 2018” is to feature where E.S.M.O makes a footprint in the commercial cancer drug development landscape. What’s so compelling with the analysis is that is constructed from an exceedingly solid knowledge-base of more than 12,500 drugs, 4,000 companies/organizations and tens of thousands of interventional clinical trials in oncology.

The hotbed of this conference is energized from an underlying cluster of roughly 300 drugs ranging from preclinical to marketed in maturity (see pipeline breakdown by stage above). Two fifths (40%) of these are Immune-Oncology drugs including Immune Checkpoint drugs, Cancer vaccines, Bispecific immunomodulators, CAR/TCR therapies and Oncolytic virotherapies. In the spotlight of this year’s Nobel Prize in Physiology or Medicine E.S.M.O 2018 features nearly 40 different immune checkpoint drugs, by far the most reported on immunotherapy and even more so if we take into account all combination therapy reports with the same. Other hot progress areas in cancer therapeutics include DNA Damage Response (DDR) drugs, epigenetic therapies, protein kinase inhibitors and antibody-drug conjugates (ADCs).

The number of targets related to the aforementioned drugs is close to 200 were the top five drug targets are: KDR/VEGFR2 (17), EGFR (15), HER2 (14), KIT (13) and FLT4 (11) (see target breakdown above).

On the contrasting end of these we find fourteen unique targets belonging to first-in-class drugs like Astellas’ enfortumab vedotin, a fully humanized monoclonal antibody that delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is highly expressed in 97% of metastatic urothelial cancer patient samples.

There is a global presence of companies at E.S.M.O 2018 ranging from big pharma to startups like Arcus Biosciences (USA), CStone Pharmaceuticals (China), Neon Therapeutics (USA), NEOMED Therapeutics 1 (Canada) and Oblique Therapeutics (Sweden).

It is noteworthy to mention that both Arcus Biosciences and Neon Therapeutics are 2016 winners of the prestigious Fierce 15 Biotech award (see 2018 cancer winners here). This prestigious award has come to symbolize novelty and being at the forefront of biotechnology development among businesses. The winners of this award are aiming at breakthroughs and big things, not at being ‘me-too’. For an example Arcus Biosciences is reporting stellar safety data from its phase 1 study of AB928, a dual antagonist of the A2aR and A2bR adenosine receptors. This development is of course only the tip of the iceberg of clinical trial reports presented at this year’s conference. In a late breaking abstract (LBA) Friday (October 19) Merrimack Pharmaceuticals will be providing more information to their previous report in June about their failed CARRIE study, evaluating the addition of istiratumab (MM-141) to standard-of-care treatment in patients with previously untreated metastatic pancreatic cancer and high serum levels of free Insulin-like Growth Factor-1 (For more LBAs see Saturday, Sunday and Monday releases). The study did not meet its primary or secondary efficacy endpoints in patients who received istiratumab in combination with nab-paclitaxel and gemcitabine, compared to nab-paclitaxel and gemcitabine alone. These results were consistent in all subgroups analyzed.

In overall the late breaking abstracts presented at ESMO (Free ESMO Whitepaper) 2018 are testament to years of rapid growth of and interest in combination therapy trials and in particular with immune-checkpoint inhibitors. On Saturday (October 20th) Genentech/Hoffman-La Roche got the world’s attention with “game changing” results from their IMpassion130 study, a global, randomised, double-blind, phase 3 study of atezolizumab + nab-paclitaxel versus placebo + nab-paclitaxel in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC). Among those who received the combination, the median survival was 21.3 months, compared with 17.6 months for those who received chemotherapy alone. The difference was not statistically significant. However, looking only at women with positive PD-L1 expressing tumors the median survival was 25 months in the combination group, versus 15.5 months with just chemotherapy. That finding has however not been analyzed statistically, and the patients are still being followed. These finds were simultaneously published in View Source">The New England Journal of Medicine and presented at ESMO 2018.

In spite of limited representation of a major therapeutic class like CAR/TCR therapies or the latest progress on targeting the CD47-SIRPA axis, all in all the ESMO (Free ESMO Whitepaper) congress is Europe’s largest clinical oncology meeting and a go-to place that acts as a sign-post on the road ahead in cancer drug development.

On October 18, 2018 Endocyte, Inc. (Nasdaq:ECYT), a biopharmaceutical company developing targeted therapeutics for cancer treatment, reported that it has entered into an agreement and plan of merger with Novartis AG ("Novartis") pursuant to which Novartis will acquire Endocyte for $24 per share, or a total equity value of approximately $2.1 billion, in cash (Press release, Endocyte, OCT 18, 2018, View Source [SID1234529960]). This offer represents a premium of 54% percent to Endocyte’s closing price of $15.56 on October 17, 2018. The transaction was unanimously approved by the board of directors of Endocyte.

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"Since acquiring exclusive worldwide rights to develop and commercialize PSMA-617 agents in 2017, the entire Endocyte team, along with our partners, have worked tirelessly to build a leading radioligand (RLT) portfolio and create value for patients and shareholders alike. We are thrilled that Novartis recognizes the potential for 177Lu-PSMA-617 to change the treatment landscape for men with metastatic castration-resistant prostate cancer (mCRPC), as well as the broader role that RLTs may potentially play in the treatment of cancer," said Mike Sherman, president and CEO of Endocyte. "The global reach and expertise of Novartis in developing and commercializing RLT therapies will be critical in efforts for patients to benefit from these therapies as quickly as possible."

Completion of the transaction is expected in the first half of 2019, subject to approval by Endocyte stockholders, antitrust and regulatory approvals and other customary closing conditions. Until that time, Endocyte will continue to operate as a separate and independent company.

Centerview Partners LLC is acting as lead financial advisor to Endocyte. Jefferies LLC is also acting as financial advisor to Endocyte. Faegre Baker Daniels LLP is acting as legal counsel to Endocyte.

Website Information

Endocyte routinely posts important information for investors on its website, www.endocyte.com, in the "Investors & News" section. Endocyte uses this website as a means of disclosing material information in compliance with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the "Investors & News" section of Endocyte’s website, in addition to following its press releases, SEC filings, public conference calls, presentations and webcasts. The information contained on, or that may be accessed through, Endocyte’s website is not incorporated by reference into, and is not a part of, this document.