On October 9, 2018 REVOLUTION Medicines, Inc. reported dosing of the first patient in a Phase 1, open-label, monotherapy dose-escalation and expansion study of RMC-4630, the company’s lead investigational drug candidate targeting the enzyme SHP2 (Press release, Revolution Medicines, OCT 9, 2018, View Source [SID1234529826]). REVOLUTION Medicines holds the IND for RMC-4630, and this trial is being conducted under the recently announced global partnership on SHP2 between REVOLUTION Medicines and Sanofi. Initiation of this clinical trial represents an important step in the company’s mission to translate frontier oncology targets on behalf of cancer patients.

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"REVOLUTION Medicines is proud to advance RMC-4630 into clinical development on behalf of patients with advanced cancers who have limited treatment options," said Stephen Kelsey, M.D., FRCP, FRCPath, president of R&D of REVOLUTION Medicines. "Our discovery of optimal inhibitors of SHP2 and elucidation of the critical role of SHP2 in the growth of certain cancers has, for the first time, suggested the potential to render these drivers of cancer clinically actionable. We are eager to advance this program by working with patients, experienced clinical investigators and our development partners at Sanofi."

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of RMC-4630 in people with relapsed, refractory solid tumors including non-small cell lung cancer and other tumor types carrying certain mutations that cause hyperactivation of the RAS-MAP kinase cell growth signaling cascade. Despite notable recent therapeutic advances in the management of lung cancer and melanoma, there remain large unmet medical needs as no targeted therapies have been approved for treating patients with solid tumors carrying these specific mutations. The study will comprise two parallel components: (1) a dose escalation study for patients with solid tumors, and (2) an expansion study for patients with tumors harboring specific mutations.

Original research led by scientists at REVOLUTION Medicines, and conducted in collaboration with researchers at the University of California, San Francisco School of Medicine, discovered that cancers caused by these oncogenic signaling proteins rely on the normal biochemical actions of SHP2. These data were first disclosed in preliminary form in 2017 via BioRxiv, and have now been published in a full peer-reviewed paper in Nature Cell Biology. They demonstrated that cancers with such "semi-autonomous" mutations may be susceptible to treatment with an inhibitor of SHP2. The trial of RMC-4630 will explore precision oncology hypotheses based on these findings at several clinical centers, including the University of California, Irvine, Chao Family Comprehensive Cancer Center.

The Role of SHP2 in Cancer

SHP2 (PTPN11), a cellular enzyme in the protein tyrosine phosphatase family, plays an important role in multiple forms of cancer and in anticancer immunity. Recently REVOLUTION Medicines reported discoveries about the regulation by SHP2 of a cell growth signaling pathway, known as the RAS-MAP kinase pathway, that frequently is hyperactive in human cancers. The research showed that some mutated forms of proteins in the RAS-MAP kinase pathway depend on SHP2 for their oncogenic activity, and that small molecule inhibitors of SHP2 designed by the company may reduce their tumorigenic effects.

About RMC-4630

RMC-4630 is a potent, selective and orally administered small molecule inhibitor of SHP2. RMC-4630 acts by stabilizing the SHP2 protein in an inactive conformation that is unable to transmit cell growth signals. RMC-4630 as a single agent was found to attenuate signal transduction through the RAS-MAP kinase cascade, reduce tumor growth and cause tumor cell death in preclinical xenograft studies of human tumors carrying select mutations in the RAS-MAP kinase pathway.

On October 9, 2018 Genomic Health, Inc. (NASDAQ: GHDX) reported that its Oncotype DX Breast Recurrence Score test has been categorized as the only "preferred" test for chemotherapy treatment decision-making for patients with node-negative early-stage breast cancer by the National Comprehensive Cancer Network (NCCN) in its 2018 guidelines for invasive breast cancer chemotherapy treatment (Press release, Genomic Health, OCT 9, 2018, View Source [SID1234529844]). The only test elevated to "strongly consider" guideline inclusion with level 1 evidence, Oncotype DX continues to be distinguished as the only genomic test predictive of chemotherapy benefit.

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NCCN’s guidelines update follows the recent publication of results of Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, led by ECOG-ACRIN Research Group. The largest adjuvant treatment breast cancer trial to date, TAILORx involved 10,273 women across 1,100 trial sites in six participating countries. The study results, published in The New England Journal of Medicine, demonstrated that the Oncotype DX Breast Recurrence Score test definitively identifies the vast majority of women with early-stage breast cancer who receive no benefit from chemotherapy, and the important minority of women for whom chemotherapy benefit can be life-saving.

Additionally, the NCCN guidelines elevated Oncotype DX into the algorithm for chemotherapy treatment of patients with micrometastases and one to three positive lymph nodes.

"We are pleased NCCN continues to clearly distinguish Oncotype DX from other genomic tests based on clinical evidence and the critical importance of predicting chemotherapy benefit," said Steven Shak, M.D., chief scientific and medical officer, Genomic Health. "This new strengthened NCCN guidelines, combined with the recent inclusion of Oncotype DX in international guidelines, demonstrates global support for Oncotype DX as the only ‘preferred’ test to guide optimal treatment based on its unique ability to predict chemotherapy benefit."

NCCN is an alliance of 21 world-leading cancer centers dedicated to improving the quality and effectiveness of care provided to patients with cancer. The 2018 guidelines were published online this week.

About Oncotype DX

The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. The company’s flagship product, the Oncotype DX Breast Recurrence Score test, is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. In prostate cancer, the Oncotype DX Genomic Prostate Score test predicts disease aggressiveness and further clarifies the current and future risk of the cancer prior to treatment intervention. With more than 900,000 patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeIQ.com, www.MyBreastCancerTreatment.org or www.MyProstateCancerTreatement.org.

On October 9, 2018 Pfizer Inc. (NYSE:PFE) reported its executive team that will report to Albert Bourla, incoming Chief Executive Officer, coincident with the commencement of his new role effective January 1, 2019 (Press release, Pfizer, OCT 9, 2018, View Source [SID1234529943]).

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"We are at a pivotal moment in Pfizer’s history, with Ian Read having positioned the company with a strong portfolio of marketed products, a deep pipeline and the clear potential to accelerate our revenue growth,"
said Bourla. "Given this opportunity to realize this accelerated growth potential, we are creating an executive team that has a proven record of success, an unwavering commitment to the patients we serve, and a clear
value creation initiative. I look forward to working with these outstanding leaders to achieve the full potential of our pipeline and deliver our next stage of growth."

Frank D’Amelio – Chief Financial Officer and Executive Vice President, Global Supply and Business Operations, will also assume the leadership for our manufacturing operations, Pfizer Global Supply (PGS).

Mikael Dolsten – Global President, Worldwide Research and Development, and Medical, will also assume oversight of the Chief Medical Officer’s role.

Michael Goettler – Global President, Established Medicines. As previously announced Michael will lead the Established Medicines business that will operate as an autonomous, stand-alone unit within Pfizer.

Angela Hwang – Group President, Pfizer Innovative Medicines, will become the Group President of Pfizer’s science-based Innovative business responsible for the entire portfolio of innovative medicines.

Rady Johnson – Executive Vice President, Chief Compliance, Quality and Risk Officer, will continue in his role as the Company’s Chief Compliance Officer.

Doug Lankler – Executive Vice President, General Counsel, will continue in his role as the company’s General Counsel.

Freda Lewis-Hall – Executive Vice President, Chief Patient Officer, will assume a new role as Pfizer’s Chief Patient Officer, deploying the resources of the company to advocate on behalf of all patients who rely on Pfizer to deliver new therapies and vaccines.

Rod MacKenzie – Executive Vice President, Chief Development Officer, will expand his responsibilities to include Pfizer’s regulatory affairs function in addition to all late stage development activities.

Dawn Rogers – Executive Vice President, Chief Human Resources Officer, will continue to lead the Human Resources team.

Sally Susman – Executive Vice President, Chief Corporate Affairs Officer, will continue to lead the Corporate Affairs function.

John Young – Group President, Chief Business Officer, will assume a new role, responsible for strategy, business development, portfolio management and valuation activities; business analytics; global commercial operations; and Patient and Health Impact, among others. Pfizer’s Consumer Healthcare business will also report to John.

Given the growing strategic importance of deploying digital technologies in research, discovery and business processes, Pfizer is appointing a Chief Digital Officer responsible for creating and implementing a strategy that accelerates and improves our digital capabilities so we can deliver more value to patients. Lidia Fonseca will join Pfizer’s
Executive Leadership Team in January 2019, as Executive Vice President, Chief Digital and Technology Officer. She is currently the Chief Information Officer and Senior Vice President at Quest Diagnostics.
Previously, she served as SVP at Laboratory Corporation of America, Executive Vice President of Global Operations and Technology at Synarc Incorporated, and held several positions of increasing responsibility at Philips Healthcare.

Executive Vice President and President, PGS, Dr. Kirsten Lund-Jurgensen, will retire at the end of the year after 19 years at Pfizer, and Executive Vice President, Strategy & Commercial Operations, Laurie Olson, will retire effective January 1, 2019, after 32 years at Pfizer.

On October 9, 2018 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported that it has raised $40 million in a Series C financing in support of further development of the company’s clinical and pre-clinical oncology programs and for general corporate purposes (Press release, Rgenix, OCT 9, 2018, View Source [SID1234529827]).

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The Series C financing was led by Lepu Medical, a publicly traded global healthcare firm, and includes Oceanpine Capital and WuXi AppTec’s Corporate Venture Fund. Existing investors also participated in the financing round, including Novo Holdings A/S, Sofinnova Partners, Alexandria Venture Investments, LLC, and the Partnership Fund for New York City’s Innovate NY Fund and associated entities.

The financing will support Phase 1b/2 clinical trials of the lead program RGX-104 in multiple cancer indications, including in checkpoint inhibitor refractory patients. It will also support early clinical development of RGX-202, a first-in-class cancer metabolism program, as well as discovery stage programs arising from the Rgenix target discovery platform.

"Lepu Medical is very pleased to make this investment in Rgenix. We truly appreciate Rgenix’s unique RNA target discovery approach in identifying various first-in-class cancer targets. We also believe RGX-104 has great potential with checkpoint inhibitors across many important cancer types," said Dr. Zhongjie Pu, PhD, Chairman and CEO of Lepu Medical. "As Lepu Medical has PD-1, PD-L1 checkpoint inhibitors and an oncolytic virus in clinical trials, we also look forward to exploring possible collaborative opportunities with Rgenix as part of our goal to develop further in the oncology market together."

"The addition of new investors to our already strong investor base is a testament to the power of our approach to develop first-in-class cancer therapeutics using the innovative Rgenix RNA target discovery platform to identify novel cancer targets," said Masoud Tavazoie, MD, PhD, and Chief Executive Officer and co-founder of Rgenix. "We are delighted to have the support of these investors and to know that they share our excitement for the work we are doing to develop these new therapies for patients who suffer from cancers of high unmet need."

RGX-104 is a first-in-class small-molecule immunotherapy that targets the Liver X Receptor (LXR) and modulates innate immunity by activating the ApoE gene. Data from a Phase 1a dose escalation of RGX-104 in advanced cancer patients demonstrated both immune-stimulatory and anti-tumor activity. Rgenix is currently enrolling patients in the Phase 1b stage of the trial in multiple cancer indications, including in combination with the checkpoint inhibitor nivolumab.

RGX-202 is a small molecule compound that suppresses gastrointestinal cancer progression by inhibiting a novel cancer metabolism pathway involved in supplying energy to cancer cells. Pre-clinical research shows the compound is active as a monotherapy and in combination with chemotherapy considered to be the standard of care. Rgenix expects to launch a Phase 1 trial of RGX-202 in 2018.

Rgenix was advised by Jefferies LLC in this Series C financing.

On October 9, 2018 Nymox Pharmaceutical Corporation (NASDAQ: NYMX) reported its important new long-term clinical trial results from the Company’s 146 patient Phase IIb NX03-0040 Fexapotide (FT) U.S. study for low grade localized prostate cancer (Press release, Nymox, OCT 9, 2018, View Source [SID1234529926]). All patients in the 78 month study had greater than or equal to 56 months from the time of enrollment, with a range of 56 to 78 months. After 78 months, the data shows that men who received the high dose Fexapotide 15mg single dosage treatment had a 73% reduction in the need for surgery or radiotherapy associated with much more favorable biopsy Gleason results compared to controls (p=.0024). There were 5% patients in the entire Fexapotide group (high dose and low dose) who showed increase in their Gleason primary pattern grade in the 78 month study, compared to controls where the incidence of grade 4 or higher primary pattern was 26.3%, a reduction of 81% (p=.0037).

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In the low grade localized prostate cancer trial reported today, Fexapotide triflutate (FT) was administered by a single painless injection directly into the prostate in a simple procedure requiring several minutes or less in an office setting without sedation or anesthesia, and guided by routine ultrasound. FT was injected into the area of the prostate where the cancer was previously detected prior to enrollment in NX03-0040. The patients were then biopsied after 6 weeks and then every 18 months, along with serial PSA measurements and long-term follow-up. After 78 months of study, high dose FT 15mg single treatment resulted in 73% less surgery or radiotherapy associated with Gleason grade progression (p=.0024), and both doses of FT (15mg and 2.5mg) as a group were overall effective (p=.0037). The 15mg dose was more effective than the lower dose. There were 5% patients in the entire FT group who showed increase in their Gleason primary pattern grade in the 78 month study, compared to controls where the incidence of grade 4 or higher primary pattern was 26.3%, a reduction of 81% (p=.0037). After 78 months all recorded instances of surgery or radiotherapy, including elective cases without Gleason upgrades, were decreased by 65.4% (p=.0014) in FT 15mg treated patients compared to the randomized control group. Numerous other parameters were significantly better in the FT treated groups compared to controls. Study NX03-0040 was undertaken starting in 2012 at 44 investigational sites across the U.S. with 146 men with the biopsy confirmed diagnosis of T1c prostate cancer, which is the most common type of low grade localized prostate cancer.

The Company expects to publish full details from this prostate cancer trial in peer review publications as well as participation in upcoming scientific presentations.

Paul Averback, CEO of Nymox, said, "These exciting new results confirm and expand the evidence for the beneficial long-term effect of a virtually painless and safe minimal administration of Fexapotide Triflutate to men with low grade localized prostate cancer. The risk of prostate cancer progression is very significantly reduced in these U.S. clinical trials, based on objective evidence from biopsies and surgery. It is important to emphasize that Fexapotide has also been shown to be associated with a major reduction in the incidence of new prostate cancer in men suffering from BPH (benign prostatic hyperplasia). This additional evidence comes from patients who received FT for their BPH in Nymox’s long-term studies of 977 men with BPH in the U.S. as part of Nymox’s pivotal Phase 3 BPH clinical program. Both 1) the long-term data reported here today involving treatment of biopsy established low grade localized cancers, and 2) the long-term prevention of new confirmed cancer in BPH patients reported previously, together indicate that FT has shown significant efficacy in men for the treatment and prevention of prostate cancer, without the risks and undesirable side effects generally associated with treatment of these conditions."

Dr. Averback added, "These strong results clearly support Management’s ongoing efforts to advance both of the Company’s 2 major clinical programs towards marketing goals. Nymox has taken the first steps toward an anticipated meeting with regulatory authorities concerning planning for registration trials for low grade prostate cancer. There is a global unmet medical need for more effective prostate treatments without the undesirable risks and often permanent side effects of current treatments."

The Company recently published and reported on the long-term safety of re-administration of Fexapotide based on re-injection studies NX02-0020 and NX02-0022 involving 344 men given Fexapotide re-injections in 2 Phase 3 multi-year re-injection safety trials. Re-injection safety data is a key necessity for injection treatments. It is expected for prostate cancer treatment that follow-up and intermittent re-treatments will be needed and desirable for many if not the majority of men who require treatment.

Low grade localized prostate cancer (T1c) represents approximately half of prostate cancers that are diagnosed, and is a very common treatment problem. The Nymox study reported today involves patients with initially Gleason grade 3+3 or lower. These patients are found to have these tumors by biopsy which is usually instituted after finding abnormalities in PSA levels, and/or after abnormal digital rectal examination of the prostate, and/or after the patient has experienced lower urinary tract symptoms or other changes.

Low grade localized prostate cancer represents a therapeutic challenge. Because of its slow growth and low initial level of malignancy, doctors and patients are often reluctant to proceed to invasive surgical treatments or radiotherapy due to the unpleasant and often permanent side effects these treatments cause in the genitourinary tract, such as sexual functional issues and/ or urinary issues. Eventually if and when the tumor progresses, invasive surgical and/or radiotherapeutic procedures become necessary, with greater risk due to the progression. Occasionally the tumors become highly malignant after variable lengths of time. These risks cause understandable anxieties and distress and many men prefer to advance to invasive therapy before running these risks of higher grade cancers.

It is widely acknowledged that a treatment alternative that can destroy or ablate the low grade cancers of the prostate without the dreaded side effects and morbidities, would be a great addition to the armamentarium of the urologist for the benefit of these patients. FT is the leading contender to deliver chemical ablation of low grade localized cancers of the prostate, without major safety risks, and to be capable of safe multiple treatments when necessary. Low grade cancers of the prostate are frequently multifocal and should be expected to require retreatments for the different cancer foci; for cancer foci that are not fully ablated; and for new cancerous foci that develop.

FT is Nymox’s first in class injectable treatment for BPH and low grade localized prostate cancer. The drug is given as a virtually painless injection with no anesthesia, analgesia or catheterization, and is an office procedure which takes a few minutes to administer. FT has been in development for BPH (prostate enlargement) for over 10 years and has been tested by expert clinical trial investigative teams in over 70 distinguished clinical trial centers throughout the US, and has been found after 7 years of prospective placebo controlled double blind studies of treatment of 977 U.S. men with BPH to not only show clinically meaningful and durable relief of BPH symptoms, but also to show a major reduction in the incidence of prostate cancer, compared to placebo and compared to the known and expected normal incidence of the disease. The same clinical BPH program has also shown in a long-term blinded placebo crossover group study an 82-95% reduction in the number of these patients who required surgery after they received crossover FT in the trial, as compared to patients who did not receive FT but instead received crossover conventional approved BPH treatments. The recent results of Phase 3 studies of Fexapotide for BPH were published earlier this year in the World Journal of Urology (May, 2018, Volume 36, Issue 5, pages 801-809) and communicated in numerous podium and symposium presentations to the American Urological Association, most recently at the Annual Meeting of the AUA in San Francisco on May 20, 2018.

Prostate cancer is the most commonly diagnosed cancer in men, other than skin cancer, and is the second leading cause of cancer death for men. Approximately 50% of prostate cancers are initially considered low risk. One of the major problems with the main current prostate treatments for localized prostate cancer (radical prostatectomy, external beam radiation, brachytherapy) is the relatively high incidence of serious sexual and other problems post-treatment. In 9 studies, Fexapotide treatment has been shown to have a negligible significant adverse effect profile post-treatment and no significant adverse effects on sexual or other functions or testosterone levels.