Bionetix, ProQinase, and MercachemSyncom announce a joint research project from target Identification to clinical study

On January 24, 2020 Bionetix, a biotech company developing novel oncology drugs; ProQinase, an oncology-focused contract research organization (CRO) recently acquired by Reaction Biology Corporation (Malvern/PA, USA); and MercachemSyncom, a chemistry CRO specializing in medicinal chemistry and comprehensive medicinal chemistry (CMC), reported they have signed a joint multiyear integrated drug-discovery project, starting from target identification (TI) up to clinical candidate selection on an undisclosed target aimed at acute myeloid leukemia (AML) (Press release, Mercachem, JAN 24, 2020, View Source [SID1234553571]). The goal of the three-party team is to advance the project to the clinical phase by 2023. The total investment sum is "significant, of multimillion Euros", but details are not being disclosed.

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"We are excited to start this new project with MercachemSyncom and ProQinase," said Dr. DooYoung Jung, CEO of Bionetix. "They have proven their quality in another project of ours, which is currently in the early development phase. When this new opportunity came up, our decision was quick and easy. We are convinced that the team will advance this program very efficiently."

Dr. Frank Leemhuis, Managing Director of MercachemSyncom, commented: "Our skilled and experienced team has a proven track record in medicinal chemistry and CMC and built valuable research assets, as the result of a consistent innovation strategy. This research project is an opportunity to build on these qualities, with the goal of serving and creating value for our client. ProQinase is ourtrusted biology partner, through years of collaboration. Together with Bionetix, we look forward to making essential contributions to this oncology program."

"We are very grateful for our long-lasting partnership with MercachemSyncom, which enables us to deliver combined top-class scientific expertise to Bionetix," said Dr. Sebastian Dempe, Chief Executive Officer of ProQinase. "This new opportunity of a multiyear collaboration, utilizing our entire breadth of oncology preclinical services, aims to develop a high-value asset for our mutual client. Working together on solid but flexible research plans, combined with efficiency, allow for short lead times and robust datageneration processes, which are key to the success of such integrated drug-discovery projects. With MercachemSyncom, we will make sure that our promises to Bionetix are met."

IMV to Host Key Opinion Leader Symposium on Role of Survivin in Cancer Biology and Potential of DPX-Survivac

On January 24, 2020 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that it will host a key opinion leader symposium on the role of survivin in cancer biology and DPX-Survivac’s potential as a targeted immunotherapeutic agent across a range of tumor types (Press release, IMV, JAN 24, 2020, View Source [SID1234553529]). The event will be held on Thursday, February 27, 2020 from 8:30 – 10:00 a.m. ET in New York, NY.

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The event will feature presentations by key opinion leaders, including:

Sally P. Wheatley, Ph.D., Assistant Professor, School of Life Sciences, University of Nottingham;

Jeannine Villella, D.O., FACOG, FACS, Chair of Gynecologic Oncology, Department of Obstetrics and Gynecology, Lenox Hill Hospital and NYU Winthrop Hospital; and

Oliver Dorigo, M.D, Ph.D., Associate Professor of Obstetrics and Gynecology, Stanford University Medical Center, Stanford University Medical Center.

Additionally, IMV management will provide a corporate update, including an overview of recent data from ongoing studies of DPX-Survivac, which is currently being evaluated in three Phase 2 studies in advanced ovarian cancer, relapsed/refractory diffuse large B-cell lymphoma and a basket of solid tumor indications. Topline results are expected from all three studies in 1H20.

A live webcast of the event will be available under "Events, Webcasts and Presentations" in the Investors section of IMV’s website and will be available for replay approximately two hours following the live event.

Kitov Pharma Receives Notice of Intention to Grant European Patent Covering the Use of NT-219 in Combination with EGFR Inhibitors

On January 24, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported receipt from the European Patent Office (EPO) of a Notice of Intention to Grant for its patent application entitled "Combinations of IRS/STAT3 Dual Modulators and Anti-Cancer Agents for Treating Cancer (Press release, Kitov Pharmaceuticals , JAN 24, 2020, View Source [SID1234553552])." The patent, which expires in 2036, covers the treatment of NT-219, the company’s novel dual inhibitor of IRS 1/2 and STAT3, in combination with EGFR antibodies and inhibitors.

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Kitov is currently advancing NT-219 in combination with cetuximab, an EGFR antibody, as a second-line or third-line therapy for the treatment of recurrent and metastatic squamous cell carcinoma of the Head & Neck Cancer (SCCHN). Kitov plans to initiate a phase 1/2 study in the second quarter of 2020.

"We believe strongly in our rationale for combining NT-219 with cetuximab and we are very pleased with this new addition to our patent estates in Europe," said Isaac Israel, Kitov’s chief executive officer. "Cetuximab is currently the only targeted FDA-approved treatment option for patients with a progressed disease following both prior platinum-based therapy and pembrolizumab. NT-219 has the potential to prevent tumor resistance and re-sensitize tumors to the anti-cancer activity of EGFR inhibitors, making this combination a very attractive drug candidate that will hopefully address the unmet medical need for recurrent and metastatic Head and Neck cancer patients."

Protein AKAP8 suppresses breast cancer metastasis

On January 24, 2020 Baylor College of Medicine reported that protein naturally produced in the body has been found to suppress breast cancer metastasis in animal models of human tumors. Researchers led by Baylor College of Medicine also found that high levels of this protein, AKAP8, predicts a better survival for breast cancer patients (Press release, Baylor College of Medicine, JAN 24, 2020, View Source [SID1234553751]).

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The findings, in the current edition of the journal Nature Communications, show that AKAP8 inhibits metastasis by interfering with the production of proteins that promote metastatic behavior in cells, and suggest strategies that may help treat metastatic cancer in the future.

"Our laboratory investigates cellular mechanisms that regulate breast cancer metastasis. In a previous study we provided the first evidence that alternative splicing, a cellular process that enables cells to switch between different forms of the same protein, can functionally control tumor metastasis," said corresponding author Dr. Chonghui Cheng, associate professor at the Lester and Sue Smith Breast Center, of molecular and human genetics and of molecular and cellular biology at Baylor.

Alternative splicing is a natural cellular process that helps cells conduct many functions, such as wound healing and embryonic development. Through alternative splicing, cells can make a large number of proteins from a limited number of genes. It would be like putting together a number of different outfits by combining in different ways a limited number of pieces of clothing. In humans, around 95 percent of all genes are processed through alternative splicing. Just recently has this process also been shown to be involved in cancer.

In that pioneering study that brought alternative splicing to the field of cancer research, Cheng and her colleagues showed that of the two distinct forms of the protein CD44 that can be produced by alternative splicing, named CD44s and CD44v, only the former contributed to cancer cell survival. These findings have been confirmed by other reports about breast cancer and also other types of cancer.

In the current study, the researchers further investigated how alternative splicing contributes to cancer metastasis by looking for proteins that regulate alternative splicing events linked to metastasis.

AKAP8 helps keep cells in a non-metastatic state
Cheng and her colleagues screened cells looking for proteins functioning as alternative splicing modulators that prevented cells from becoming metastatic. They identified a set of proteins that were potentially key for tumor metastasis regulation and focused on AKAP8.

"We studied AKAP8 in metastatic breast cancer animal model systems of cancer cells from human patients," Cheng said. "We found that depletion of the AKAP8 protein in patient cancer cells promoted breast cancer metastasis in these mouse models. Furthermore, providing an external source of AKAP8 inhibited metastasis."

Taking it all together, the results support AKAP8 as an important regulator of alternative splicing events linked to tumor metastasis. It is not only able to predict metastatic breast cancer outcomes in patients, but also can inhibit metastatic breast cancer progression in animal models.

Cheng and her colleagues continued their investigations to determine how AKAP8 mediated its metastasis-suppressing effects. They discovered that, in addition to modulating alternative splicing of CD44, AKAP8 also regulated the alternative splicing of another protein called CLSTN1. In this case, of the two forms of CLSTN1, named CLSTN1S and CLSTN1L, AKAP8 tipped the balance toward the production of the former, which was associated with preventing cells from progressing toward a metastatic state. This was a previously unknown function of CLSTN1.

"We think that modulators of alternative splicing participate in a delicate balancing act of many different cellular proteins, such as CD44 and CLSTN1. Two types of modulators play a part in keeping the balance. One type, like AKAP8, modulates alternative splicing toward the production of proteins that help cells remain in a normal state. The other type tips the balance toward proteins that promote metastatic transformation," Cheng said. "If the balance is disturbed, tumor progression can be promoted. By investigating how the balance is kept and the factors that disturb the balance, we hope to understand a new layer of regulation of tumor metastasis and gain insights that could lead to treatments for metastatic cancer, a deadly disease."

Other contributors to this work include Xiaohui Hu, Samuel E. Harvey, Rong Zheng, Jingyi Lyu, Caitlin L. Grzeskowiak and Kenneth L. Scott at Baylor; and Emily Powell and Helen Piwnica-Worms at The University of Texas MD Anderson Cancer Center, Houston.

This research was supported in part by grants from the US National Institutes of Health (5F30CA196118, R01 CA182467, R01GM110146 and R35GM131876) and CPRIT Scholar in Cancer Research grant RR160009.

Genentech Provides an Update on Phase III Study of Tecentriq in People With Muscle-invasive Urothelial Cancer

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