On March 18, 2019 Cold Genesys, Inc., a clinical-stage biopharmaceutical company focused on the development of novel immunotherapies, reported the closing of a $22 million Series C preferred stock financing (Press release, Cold Genesys, MAR 18, 2019, View Source [SID1234534429]). New investors participated in the round, including lead investor, ORI Healthcare Fund L.P. ("ORI Fund"), with participation from Perseverance Capital Management.

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The financing will accelerate the growth of Cold Genesys’ ongoing clinical programs and the continued advancement of its lead oncolytic immunotherapy CG0070, which has completed a Phase 2 study (BOND2) and demonstrated clinical safety and efficacy in over 100 patients to date for the treatment of Non-Muscle Invasive Bladder Cancer (NMIBC).

"Cold Genesys has reached an exciting stage in its development, and this financing demonstrates continued investor confidence in our leadership and future in the field of oncolytic immunotherapy," said Arthur Kuan, CEO of Cold Genesys. "We have made significant progress within the last year, from new leadership appointments to our partnership with Merck to evaluate their anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in combination with CG0070 in a Phase 2 clinical study. Our robust pipeline based on our oncolytic immunotherapy platform, partnerships with leading institutions, and key advancements in our clinical program, demonstrate our commitment to rapidly advancing therapies that will change the lives of patients with bladder cancer and other solid tumors."

"We are a strong believer in using the oncolytic immunotherapy approach in both monotherapy and combo therapy to combat cancer," said Simone Song, Senior Partner of ORI Fund. "We are very fortunate to have the opportunity to work with an outstanding firm such as Cold Genesys which has completed the Phase 2 study for NMIBC. We have confidence that Cold Genesys will fulfill the unmet medical need for NMIBC, and we also hope that Cold Genesys can become a platform company to benefit patients with various types of solid tumors by applying its oncolytic immunotherapy expertise."

On March 18, 2019 BioTime, Inc. (NYSE American and TASE: BTX), a clinical-stage biotechnology company focused on degenerative diseases, reported that Brian M. Culley, Chief Executive Officer, will be presenting at the Oppenheimer & Co. 29th Annual Healthcare Conference on March 20th, 2019 at 2:45pm Eastern Time at the Westin New York Grand Central in the Track 2 Room in New York, NY (Press release, BioTime, MAR 18, 2019, View Source;p=RssLanding&cat=news&id=2391558 [SID1234534463]).

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Interested parties can access a live audio webcast on the Events and Presentations section of BioTime’s website and an archived presentation will be available for 30 days. Interested parties may follow @OppenheimerCo on Twitter and use #OPCOHealthcare for the latest conference updates.

On March 18, 2019 Leap Therapeutics, Inc. (Nasdaq:LPTX) reported the presentation of clinical data from its ongoing Phase 2 clinical trial of DKN-01 in patients with advanced gynecological malignancies at the Society of Gynecologic Oncology 50th Annual Meeting on Women’s Cancer (Press release, Leap Therapeutics, MAR 18, 2019, View Source [SID1234534414]). Patients, including those with carcinosarcoma and Wnt pathway alterations, have experienced partial responses and durable clinical benefit in both the monotherapy and combination arms of the study. The complete data set will become available in the coming months as the most recently enrolled patients have yet to be evaluated. The complete poster is available on Leap’s website at View Source

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"We are very pleased with the single agent and combination activity of DKN-01 in this heavily pre-treated population. Allowing patients to achieve partial responses and durable stable disease with a favorable safety profile reflects meaningful clinical benefit," commented Rebecca C. Arend, M.D., Ph.D., Department of Obstetrics and Gynecology at the University of Alabama at Birmingham School of Medicine. "With the rapid enrollment of this study since the beginning of the year, we are looking forward to robust data maturing during the year."

"It is encouraging to see the mechanism-based strategy of enriching the study with patients with Wnt pathway alterations lead to impressive clinical outcomes," commented Michael Birrer, M.D., Ph.D., Director of the Comprehensive Cancer Center at the University of Alabama at Birmingham. "We are also particularly interested in the early activity in carcinosarcoma patients, who are in need of new and better treatment options."

· DKN-01 single agent partial response: Twenty-one patients (who had previously received one to ten lines of therapy) have been enrolled in two monotherapy arms of the study. Twelve patients are currently evaluable. One patient has experienced a partial response (PR), and six patients have had stable disease (SD) for greater than six weeks. Seven patients have been recently enrolled and have not yet had their first imaging assessment. This study marks the third different tumor type where DKN-01 has had single agent activity.

·Partial response and tumor reductions in DKN-01/Paclitaxel combination: Forty-one patients (who had previously received one to nine lines of prior therapy) have been enrolled in two combination arms of the study. Twenty-one patients are currently evaluable. One patient has experienced a PR, and fifteen patients have had SD for greater than six weeks. Thirteen patients have been recently enrolled and have not yet had their first imaging assessment.

·Patients whose tumors had confirmed Wnt pathway alterations experienced a greater duration of clinical benefit: In eight evaluable monotherapy patients with confirmed Wnt pathway alterations, one patient has experienced a PR and four have had SD. In the fourteen evaluable combination therapy patients, one patient has experienced a PR and seven have had SD. The patient with a partial response on DKN-01 combination therapy has a tumor with a CTNNB1 mutation. Tumor CTNNB1 mutations stabilize the transcription factor beta-catenin and are correlated with increased levels of DKK1 and poor clinical outcomes. In this study, eight CTNNB1 patients are evaluable, and six experienced clinical benefit.

· Carcinosarcoma partial response leads to new expansion cohort at higher dose: Carcinosarcoma is a rare and difficult-to-treat form of uterine cancer. Four carcinosarcoma patients have been enrolled, and the three evaluable patients had tumor reductions and one experienced a PR. To explore a new treatment option for these patients, the Company will expand the study and provide a higher dose of DKN-01 as a monotherapy and in combination with paclitaxel.

About P204

The P204 study is a Phase 2 basket study evaluating DKN-01 as a monotherapy and in combination with paclitaxel in patients with relapsed/refractory endometrioid endometrial cancer (EEC) or endometrioid ovarian cancer (EOC). The study contains four groups and is designed to evaluate the efficacy, safety, and pharmacodynamics of DKN-01 monotherapy and combination therapy in both EEC and EOC, with each group following a 2-stage Simon Minimax design. The study will enroll approximately 94 patients, of which approximately 50% will be required to have documented activating mutations of beta-catenin or other Wnt signaling alterations.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin signaling, a signaling pathway frequently implicated in tumorigenesis and suppressing the immune system. DKK1 has an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK ligands on tumor cells.

On March 18, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) approved Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Genentech, MAR 18, 2019, View Source [SID1234534430]). This approval is based on results from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS] = 12.3 versus 10.3 months; hazard ratio [HR] = 0.70, 95 percent CI: 0.54-0.91; p=0.0069) in the intention-to-treat (ITT) population. The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95 percent CI: 0.62-0.96; p=0.017). Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.

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"Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy."

"Extensive-stage small cell lung cancer is a highly aggressive form of lung cancer, which until now, has seen limited treatment advances over the last 20 years," said Andrea Ferris, president and CEO of LUNGevity Foundation. "Today’s approval of Tecentriq is an important step forward in ensuring that people across the spectrum of lung cancer types have effective new therapies."

Results from the Phase III IMpower133 study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.

Tecentriq is also approved in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. Additionally, Tecentriq is approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving Tecentriq.

For those who qualify, Genentech offers patient assistance programs for people taking Tecentriq through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (866) 422-2377. More information is also available at View Source

About the IMpower133 study

IMpower133 is a Phase III, multicenter, double-blinded, randomized placebo- controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) versus chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve people with ES-SCLC. The study enrolled 403 people who were randomized equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were progression-free survival (PFS) as determined by the investigator using RECIST v1.1 and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below.

Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 versus 10.3 months; HR=0.70, 95 percent CI: 0.54-0.91; p=0.0069) in the ITT population.
The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95 percent CI: 0.62-0.96; p=0.017).
Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq. Serious adverse reactions occurred in 37 percent of people receiving Tecentriq plus chemotherapy compared with 35 percent of people receiving chemotherapy alone. The most common adverse reactions (≥20 percent) in people receiving Tecentriq plus chemotherapy were feeling tired or weak (fatigue/asthenia; 39 percent), nausea (38 percent), hair loss (alopecia; 37 percent), decreased appetite (27 percent), constipation (26 percent) and vomiting (20 percent).
About lung cancer

According to the American Cancer Society, it is estimated that more than 228,000 Americans will be diagnosed with lung cancer in 2019. Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 84 percent of all lung cancer cases, and SCLC accounting for approximately 13 percent of all cases. The majority (approximately 70 percent) of people with SCLC are diagnosed with ES-SCLC.

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. Indications (pronounced ‘tē-SEN-trik’)

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 "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. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used with bevacizumab and the chemotherapy medicines carboplatin and paclitaxel as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
your tumor does not have an abnormal "EGFR" or "ALK" gene
Tecentriq may be used when your lung cancer:
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working, and
if your tumor has an abnormal "EGFR" or "ALK" gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.
A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound when your breast cancer:
has spread or cannot be removed by surgery, and
your cancer tests positive for "PD-L1"
The approval of Tecentriq in these patients is based on a study that measured progression-free survival. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called small cell lung cancer (SCLC).

Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment when your lung cancer:
is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown
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 your skin or the whites of your 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 your 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 your 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
nausea
cough
shortness of breath
decreased appetite
The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite
The most common side effects of Tecentriq when used in triple-negative breast cancer with paclitaxel protein-bound include:

hair loss
tingling or numbness in hands or feet
feeling tired
nausea
diarrhea
low red blood cells (anemia)
constipation
cough
headache
low white blood cells
vomiting
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. Patients should call their doctor for medical advice about side effects.

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 20 investigational medicines, 10 of which are in clinical trials. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit View Source

About Genentech in Lung Cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On March 18, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, reported at R&D Day in New York the continued progress of the its pipeline of proprietary CAR-T therapies for the treatment of hematological malignancies and solid tumors, based on its short hairpin RNA (shRNA) platform (Press release, Celyad, MAR 18, 2019, View Source [SID1234534464]).

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"We are very pleased with the recent progress of our preclinical CAR-T pipeline," noted Dr. Christian Homsy, CEO of Celyad. "Together with CYAD-101, our next generation allogenic shRNA platform should allow us to leapfrog the competition in the allogeneic CAR-T landscape. In addition, CYAD-02 has shown encouraging preclinical data of increased CAR-T cell expansion, persistence and anti-tumor efficacy. We continue to tap into our deep expertise and knowledge in cell therapy manufacturing and our all-in-one vector approach provides tremendous flexibility, versatility and efficiency in the design of novel, CAR-T therapies."

Corporate Updates

Lead asset CYAD-01 continues to advance in clinical trials for the treatment of patients with relapsed/refractory (r/r) acute myeloid leukemia (AML). The Company reported that additional dosing and schedule optimization are under evaluation in the THINK Phase 1 trial. In addition, the Company reported that interim data from the DEPLETHINK Phase 1 trial evaluating CYAD-01 following preconditioning chemotherapy shows the CAR-T cell therapy is well-tolerated at the initial dose levels following preconditioning chemotherapy. Future clinical updates from the Phase 1 THINK and DEPLETHINK trials are anticipated by mid-2019.
Company also highlighted its operational excellence for 2018 including a 94% manufacturing success rate and a twofold increase year-over-year in the number of patients treated.
shRNA Platform

In October 2018, Celyad announced it had entered into an exclusive agreement with Horizon Discovery Group for the use of its shRNA technology to generate a novel, next-generation, non-gene-edited allogeneic platform for CAR-T therapies. Horizon Discovery’s SMARTvector technology to express shRNA optimized by Celyad provides an alternate method to knockout the TCR complex in allogeneic CAR-T therapies compared to gene editing techniques as well as the specificity to target a broad range of proteins.
Utilization of the shRNA platform allowed the Company to develop the next generation of autologous, NKG2D-based CAR-T candidate, CYAD-02, and the novel, non-gene edited allogeneic CYAD-200 series of CAR-T candidates.
In addition, the shRNA platform complements the Company’s strong intellectual property of six U.S. patents related to allogeneic T-cell technology and producing TCR deficient cells expressing a CAR construct.
Autologous CAR-T candidate: CYAD-02

CYAD-02 incorporates shRNA technology to target NKG2D ligands MICA/MICB. In preclinical AML models, CYAD-02 shows an encouraging increase in in vitro proliferation and in vivo persistence and anti-tumor activity. The Company plans to generate additional preclinical proof-of-concept data for the program throughout 2019 and plans to submit an Investigational New Drug (IND) application for CYAD-02 in first half 2020.
Non-gene edited allogeneic CAR-T candidates: CYAD-200 series

Celyad utilizes two technologies based on non-gene edited approaches to modulate the T-cell receptor (TCR) complex to generate allogeneic CAR-T therapies. The first approach utilizes our TCR-inhibitor molecule (TIM) and is tailored to our NKG2D-based CAR-T clinical candidate CYAD-101. The second approach leverages shRNA technology exclusively licensed from Horizon Discovery to target the CD3ζ component to knockdown the expression of the TCR/CD3 complex on the surface of the T-cell.
In vivo data demonstrate that shRNA targeting of CD3ζ effectively protects against Graft-versus-Host Disease (GvHD) to a level equivalent to CRISPR-Cas9 based knock-out. Furthermore, results from preclinical tests show significant increase in persistence of allogeneic T cells using shRNA targeting when compared to gene editing technologies, such as CRISPR-Cas9.
Celyad announced plans to develop three disruptive first-in-class non-gene-edited allogenic CAR-T candidates leveraging the shRNA SMARTvector platform, including:
CYAD-211: B-cell maturation antigen (BCMA) targeting CAR-T therapy for the treatment of multiple myeloma, which is expected to enter the clinic by mid-2020.
CYAD-221: CD19 targeting CAR-T therapy for the treatment of B-cell malignancies, which is expected to enter the clinic by late 2020.
CYAD-231: Dual specific CAR-T targeting NKG2D and an undisclosed membrane protein, which is expected to enter the clinic by early 2021.
In addition, the company continues to investigate additional undisclosed targets using the shRNA platform to pair with CARs to develop, differentiated next-generation cell therapies for the treatment of both hematological malignancies and solid tumors.