On January 24, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the Phase III IMvigor010 study evaluating Tecentriq (atezolizumab) as an adjuvant (after surgery) monotherapy treatment did not meet its primary endpoint of disease-free survival (DFS) compared to observation in people with muscle-invasive urothelial cancer (MIUC) (Press release, Genentech, JAN 24, 2020, View Source [SID1234553471]). Safety for Tecentriq appeared consistent with the known safety profile of the medicine, and no new safety signals were identified.

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"Reducing the risk that muscle-invasive urothelial cancer will recur after surgery is very difficult, and we are disappointed that we were not able to significantly prolong disease-free survival," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We remain committed to exploring the potential benefits of immunotherapy for more people with early cancers."

The goal in treating MIUC early is to reduce the risk of the disease recurring or spreading to other parts of the body. More treatment options following surgery are needed as approximately half of people with MIUC will develop a recurrence of their disease within two years of surgery.

In addition to ongoing Phase III studies in early and advanced bladder cancer, Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMvigor010 study

IMvigor010 is a global Phase III, open-label, randomized, controlled study designed to evaluate the efficacy and safety of adjuvant treatment with Tecentriq compared with observation in 809 people with MIUC, who are at high risk for recurrence following resection. The primary endpoint is DFS as assessed by investigator, which is defined as the time from randomization to invasive urothelial cancer recurrence or death.

About bladder cancer

According to the American Cancer Society (ACS), it is estimated that more than 81,000 Americans will be diagnosed with bladder cancer in 2020. Urothelial cancer is the most common type of bladder cancer, accounting for about 90-95% of all cases. MIUC is a type of urothelial cancer that has spread into the muscle wall of the bladder, ureter, or renal pelvis. Approximately 25% of people newly diagnosed with bladder cancer are diagnosed with muscle-invasive disease, which is associated with a poorer prognosis than non-MIUC.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Bladder Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your cancer tests positive for "PD-L1", or
you are not able to take chemotherapy that contains any platinum regardless of the levels of "PD-L1" status, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information
What is the most important information about Tecentriq?
Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

feeling tired or weak
nausea
cough
shortness of breath
decreased appetite
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or View Source
Report side effects to Genentech at 1-888-835-2555.

Please visit View Source for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Genentech in personalized cancer immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 10 cancer immunotherapy medicines across 70 clinical trials alone or in combination with other medicines. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit View Source

On January 24, 2019 The Simmons Comprehensive Cancer Center reported constantly finding drug combinations that help fight drug-resistant cancers (Press release, The Simmons Comprehensive Cancer Center, JAN 24, 2020, View Source [SID1234553752]). Researchers at the UT Southwestern Medical Center appeared to have found a new one using already approved drugs .

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The investigators were studying data from a "molecularly guided trial" in which breast cancer patients with HER2 mutations received neratinib (Puma Biotechnology’s Nerlynx), which is a HER2 inhibitor. If the disease progressed despite treatment, the researchers sequenced the DNA of the tumors. They found in the laboratory that an effective approach to battling eventual resistance to neratinib was another drug, everolimus (Novartis’ Afinitor). Everolimus is a TORC1 inhibitor often used to treat other forms of breast cancer.

"This finding may give clinicians an effective response to neratinib resistance," said Carlos L. Arteaga, director of the Simmons Cancer Center at UT Southwestern and corresponding author of the research. "That could make a real difference for patients with breast, ovarian, lung, and other cancers harboring HER2 mutations."

HER2 mutations are known to drive breast cancer and other cancers. The researchers focused on a signaling network driven by TORC1. The network is the pathway where HER2-mutant cancers develop resistance to neratinib.

"We consistently noted activation of TORC1 signaling as a mechanism of resistance to neratinib across different types of HER2-mutant cancers," said Dhivya Sudhan, a postdoctoral research fellow at the Harold C. Simmons Comprehensive Cancer Center. "Different cancer types used different strategies to escape neratinib, but they all converged on TORC1 signaling."

They evaluated the research in data from clinical trials across the country as well as in neratinib-resistant cells and tumors grown in the laboratory. Some patients, they found, already had a mutation that could possibly activate the TORC1 pathway. Others developed it. Both groups could potentially benefit from everolimus, which would extend the patient’s ability to respond to neratinib.

At this time the combination worked in cell lines, in organoids developed from patient-derived tumors, and in mice with the HER2 mutant tumors. They hope to begin testing the two-drug combo in human clinical trials.

The research was published in the journal Cancer Cell.

Earlier this week, researchers at the Broad Institute of MIT and Harvard tested about 4,518 drugs on 578 human cancer cell lines. They discovered that almost 50 had previously unrecognized anti-cancer properties. The drugs ranged from treatments for diabetes, inflammation, alcoholism and arthritis in dogs.

"We thought we’d be lucky if we found even a single compound with anti-cancer properties, but we were surprised to find so many," said Todd Golub, chief scientific officer and director of the Cancer Program at the Broad.

The research leveraged the Broad’s Drug Repurposing Hub. This Hub is made up of more than 6,000 existing drugs and molecules the U.S. Food and Drug Administration (FDA) has either already approved or have been shown to be safe in clinical trials. At the time the group conducted their study, there were 4,518 compounds in the Hub.

"Most existing cancer drugs work by blocking proteins, but we’re finding that compounds can act through other mechanisms," Steven Corsello said. Corsello is an oncologist at Dana-Farber Cancer Institute, founder of the Drug Repurposing Hub, member of the Golub lab and first author of the study, which was published in the journal Nature Cancer.

For example, some of the drugs activated a protein or stabilized a protein-protein interaction. Almost a dozen of the non-cancer drugs killed cancer cells expressing the PDE3A protein by stabilizing the PDE3A and SLFN12 protein interaction. This was an unknown mechanism.

Many of the drugs killed cancer cells by interacting with a previously unrecognized molecular target. One example is the drug tepoxalin, used to treat osteoarthritis in dogs. But the drug killed cancer cells by interacting with an unknown target in cancer cells that overexpress the MDR1 protein, which is linked to resistance to chemotherapy drugs.

The researchers were further able evaluate the cell line’s genomic features and predict which drugs could kill each cell line. Those genomic features included mutations and methylations levels, which were available in the CCLE database.

On January 24, 2020 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that it will host a webcast at 11am (CET) on Monday, January 27th 2020 where CEO Jakob Lindberg will present and explain melflufen’s mechanism of action (Press release, Oncopeptides, JAN 24, 2020, View Source [SID1234553532]).

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Conference call for investors, analysts and the media, Monday, January 27th 2020, at 11 (CET).

The conference call will also be streamed on the corporate website www.oncopeptides.com and via the link below.

View Source

The presentation will be available at:

www.oncopeptides.com / Investor Relations / Presentations / Presentation webcast melflufen mechanism-of-action/

For more information, please contact:
Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 70 853 72 92

This information was submitted for publication at 18.30 CET January 24, 2020.

About melflufen

Melflufen is a novel peptide-drug conjugate that rapidly delivers a cytotoxic payload into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

On January 24, 2020 Sun BioPharma, Inc. (OTCQB: SNBP), a clinical-stage biopharmaceutical company developing disruptive therapeutics for the treatment of people with pancreatic cancer, reported initial Phase 1 clinical data for SBP-101, which was presented in a poster session at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Gastrointestinal Cancers Symposium (Press release, Sun BioPharma, JAN 24, 2020, View Source [SID1234553533]). SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI), a metabolic pathway of critical importance in cell function in multiple tumor types. Based upon the study data presented today, the adverse event profile of SBP-101 at the optimal dose level was manageable and an expansion study in patients with pancreatic ductal adenocarcinoma (PDA) is planned to begin during the second quarter of 2020.

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"We are excited about the early results from this Phase 1 trial, which suggest improved activity of SBP-101 in combination with gemcitabine and nab-paclitaxel, along with a tolerable adverse event profile," said Dr. Dusan Kotasek, Director, Clinical Research at Adelaide Cancer Centre and a key Principal Investigator in both the monotherapy and combination therapy studies of SBP-101. "Pancreatic ductal adenocarcinoma is an area of incredibly high unmet medical need, and by evaluating SBP-101 with the current standard of care, we hope to be able to offer patients an improved therapeutic option."

Preliminary Results Demonstrate Tolerability and Clinical Activity in Metastatic Treatment-Naïve Patients

As of the data cut off date of January 4, 2020, the addition of SBP-101 to the combination of gemcitabine plus nab-paclitaxel did not increase the frequency of grade 3/4 hematologic adverse events, peripheral neuropathy, nausea or diarrhea when compared to historical control data for patients who were treated with gemcitabine plus nab-paclitaxel. The most common adverse events (all grades) attributed to treatment with SBP-101 were fatigue, elevated LFTs, and injection site pain.

The most common grade 3/4 adverse event was elevation in liver function tests, which in most cases was asymptomatic, and in all cases reversed when SBP-101 was interrupted and decreased or discontinued.

Study results in evaluable subjects enrolled in the two highest dose cohorts (N=13) demonstrated an overall response rate (ORR) of 62%, including 8 partial responses (PRs). The disease control rate (DCR) was 85% by RECIST criteria. Eleven subjects in those cohorts (69%, N=16) saw a maximum decrease in CA 19-9 of more than 60%. As of January 4, 2020, 8 of 16 subjects remained on study. Median duration of response, progression free survival and overall survival had not been reached.

Phase 1a/1b Trial Design

This ongoing multicenter, open label, Phase 1 trial enrolled 20 patients with pancreatic ductal adenocarcinoma (PDA) across three dose cohorts. Study participants received a subcutaneous dose of SBP-101 at 0.2, 0.4 or 0.6 mg/kg on days 1-5 of each 28-day cycle, in addition to intravenous doses of 1000 mg/m2 of gemcitabine and 125 mg/m2 of nab-paclitaxel on days 1, 8 and 15. The goal of this study was to determine a recommended dose of SBP-101 for further development. Endpoints include safety, tolerability, and pharmacokinetics, in addition to early measures of efficacy including ORR as measured by RECIST, and CA19-9 levels. Based upon preliminary safety and efficacy signals, the protocol was amended to follow subjects for progression-free survival (PFS) and overall survival (OS).

Poster Presentation Information

Efficacy of SBP-101, in combination with gemcitabine and nab-paclitaxel, in first-line treatment of metastatic pancreatic ductal adenocarcinoma.
Friday, January 24, 2020, 12:00 PM to 1:30 PM and 4:30 PM to 5:30 PM
Abstract 710, Board K21
Poster Session B: Hepatobiliary Cancer, Neuroendocrine/Carcinoid, Pancreatic Cancer, and Small Bowel Cancer
American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Gastrointestinal Cancers Symposium

About SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI), a metabolic pathway of critical importance in multiple tumor types. Sun BioPharma licensed SBP-101 from the University of Florida Research Foundation in 2011. The molecule has been shown to be a highly effective tumor growth inhibitor in preclinical studies of human pancreatic cancer models, demonstrating superior and complementary activity to existing FDA-approved chemotherapy agents. SBP-101 has demonstrated activity against primary and metastatic disease in clinical trials of patients with pancreatic cancer. The safety data and PMI profile observed in Sun BioPharma’s previously completed first-in-human dose escalation study of SBP-101 provides support for evaluation of SBP-101 in combination with current standard pancreatic cancer treatment.

On January 24, 2020 Beam Therapeutics, a biotechnology company developing precision genetic medicines through base editing, reported the promotion of chief scientific officer Giuseppe "Pino" Ciaramella, Ph.D., to president. Dr. Ciaramella will continue his role as chief scientific officer (Press release, Beam Therapeutics, JAN 24, 2020, View Source [SID1234553515]).

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"Pino has been an exceptional leader at Beam from day one, leading the growth of our base editing platform and pipeline," said John Evans, chief executive officer of Beam. "Pino will be at the forefront of our efforts to advance base editing as a potentially new therapeutic option for a range of genetically-defined diseases. We congratulate Pino on this well-deserved promotion to lead the next stage in the evolution of Beam."

Dr. Ciaramella has served as Beam’s chief scientific officer since February 2018, bringing more than 20 years of drug discovery experience. Throughout his career, he has held several leadership roles, with a particular focus in the fields of antivirals, immunology and biotherapeutics. Prior to joining Beam, Dr. Ciaramella was the chief scientific officer of the infectious disease division of Moderna Therapeutics, where he was instrumental in generating some of the first mRNA vaccines to be dosed in humans, several of which are progressing through clinical studies. Before Moderna, he served in senior leadership roles at Astra Zeneca and at Boehringer Ingelheim, where he was responsible for external R&D and was a member of the research leadership team. Prior to Boehringer Ingelheim, he spent 14 years at Pfizer in the U.K., where he held several discovery leadership positions, including head of biotherapeutics, head of antivirals and head of lead discovery. Dr. Ciaramella holds a Ph.D. in biochemistry and molecular biology from University College London.