On April 16, 2019 Phoenix Molecular Designs (PhoenixMD), a privately-held biotechnology company designing precise cancer therapeutics by targeting essential kinases, reported that it has entered into a collaboration with STA Pharmaceutical Co., Ltd (STA), a WuXi AppTec group company, to manufacture the PMD-026 needed for IND-enabling toxicology studies and a Phase I study in women (Press release, Phoenix Molecular Designs, APR 16, 2018, View Source [SID1234536961]).

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Under the terms of the collaboration agreement, STA will become a new manufacturing partner for PhoenixMD for their platform of kinase inhibitor drug candidates to treat a wide range of unmet medical needs, with an initial focus on triple negative breast cancer (TNBC). STA will be responsible for the early manufacturing work through their GMP-certified site in San Diego, CA. Through these collaborative efforts, PhoenixMD expects to file an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA) for PMD-026.

Dr. Minzhang Chen, CEO of STA, commented, "We are excited to manufacture PMD-026 and enable Phoenix MD to advance this novel RSK inhibitor to shrink tumors in Phase 1 studies in women."

"We’re thrilled to collaborate with STA, a global leader in drug development and manufacturing, who has helped us achieve an important milestone in the efficient and scalable manufacturing of PMD-026," said Sandra E. Dunn, CEO PhoenixMD. "Through this work, we have demonstrated that PMD-026 has the potential to be disease-modifying with its ability to block the RSK pathway signaling and initiating significant tumor shrinkage of up to 70% in TNBC xenograft models. Looking ahead, we expect to build upon this progress and file an IND for PMD-026, with the ultimate goal of confirming these revolutionary results in women suffering from TNBC."

Gerrit Los, CSO of PhoenixMD added, "It is critical to have a manufacturing partner at this stage of development for PMD-026. This collaboration will allow us to move PMD-026 into IND enabling toxicology studies and to get ready for a successful IND filing. Importantly, it provides us the security to have access to GMP quality API when we are ready to start our Phase I study."

About Triple Negative Breast Cancer (TNBC) and RSK Kinases

Approximately 400,000 cases of TNBC are diagnosed every year worldwide and it is one of the most difficult breast cancer subtypes to treat due to lack of effective, targeted therapies. TNBC also claims the lives of young women more than any other type of breast cancer due to a lack of understanding around the therapeutic bullseye. It is also a very heterogeneous disease, therefore a common denominator across TNBC types was necessary to identify the bullseye. Through genome-wide screens, RSK was identified as the prime target for TNBC by scientists at PhoenixMD. Currently, there are still no targeted therapies available for TNBC.

There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance.

RSK1 and RSK2 have been proven critical to the survival of patients with TNBC. Over 90% of primary TNBC express high levels of RSK1 and RSK2. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. PhoenixMD, with its novel, targeted approach, is focused on creating patented cancer RSK inhibitors and companion diagnostics for cancer indications – initially in breast cancer – with the potential to treat blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

Currently, there are no approved targeted therapies for TNBC, although several drugs are subject to research studies and clinical trials. PhoenixMD is addressing this unmet medical need through a novel, targeted approach by inhibiting critical kinases, such as RSK1-4, a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. For this target, PhoenixMD developed PMD-026, a first-in-class, specific RSK inhibitor that blocks downstream signaling of RSK and induces apoptosis.

On April 16, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported preliminary data from the Toca 6 Phase 1 trial of Toca 511 & Toca FC in advanced solid tumors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in Chicago (Press release, Tocagen, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342699 [SID1234525821]). The poster was presented by Jaime Merchan, M.D., director, Phase 1 clinical trials program at Sylvester Comprehensive Cancer Center, part of UHealth, the University of Miami Health System; associate professor of medicine at the University of Miami Miller School of Medicine.

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As of the data cutoff date of March 27, 2018, 7 patients with advanced solid tumors received Toca 511 & Toca FC intravenously (IV). Among these patients, 4 also received Toca 511 via intratumoral administration.

Data highlights are below. The poster will be placed on Tocagen’s website following its presentation.

Cancer-selective expression of the Toca 511 transgene following IV administration was demonstrated in metastatic tumors of 5 patients for whom tissue analyses had been completed, indicating successful delivery of the retroviral replicating vector (RRV).
Viral RNA, DNA and cytosine deaminase (CD) protein expression was detected in liver metastases from 4 patients with colorectal cancer and retroperitoneal lymph node metastases from 1 patient with pancreas cancer.
Toca 511 was cleared from blood plasma within 6 weeks following IV administration, indicating the virus is well controlled outside of tumors.
Toca 511 & Toca FC were well tolerated, supporting the favorable safety profile of the product candidate.
"The preliminary data from the Toca 6 trial represent an important milestone for our RRV platform technology and lead product: for the first time we have demonstrated Toca 511’s ability to selectively infect metastases from solid tumors other than glioma following IV delivery, opening potential expansion opportunities for our lead product," said Marty Duvall, chief executive officer of Tocagen. "In the year ahead we plan to initiate studies that evaluate the efficacy of our regimen in patients with advanced cancers."

Additional data from Tocagen’s Phase 1 trial demonstrating the immune profile of the tumor microenvironment is associated with response in patients with recurrent high-grade glioma who received Toca 511 & Toca FC via resection will be presented on Wednesday, April 18, 8:00 a.m. – 12:00 p.m. CT (Abstract: 5630). The poster will also be placed on Tocagen’s website following the presentation.

About Toca 6

Toca 6 is an ongoing Phase 1b study evaluating Toca 511 & Toca FC in patients with advanced solid tumors. The study will evaluate the safety and presence of Toca 511 genes in tumors of patients with widely disseminated disease, immunologic activity in blood and tumor and clinical activity such as tumor response and clinical benefit. More information can be found at www.tocagen.com/toca6 or by searching clinicaltrials.gov using the clinical trial identifier NCT02576665.

About Toca 511 & Toca FC

Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511, and an investigational small molecule, Toca FC. Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, only infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

On April 16, 2018 Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, is pleased to report additional information from the Company’s successfully completed Phase 2 clinical trial of Brilacidin-OM (see NCT02324335) for the indication of decreasing the incidence of Severe Oral Mucositis (SOM) (WHO Grade ≥3) in Head and Neck Cancer (HNC) patients receiving chemoradiation (Press release, CellCeutix, APR 16, 2018, View Source [SID1234525812]).

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These additional data align with previously released Brilacidin-OM results showing a risk reduction in the incidence of SOM, including up to an 80.3% risk reduction in the incidence of SOM among patients receiving more aggressive chemotherapy. Other previously released results indicate Brilacidin-OM also delayed onset of SOM. The Company is developing Brilacidin-OM under FDA Fast Track designation as a convenient, and clearly differentiated, therapy aimed to decrease incidence of SOM.
Initial Instance Duration of SOM was defined as the number of days from initial WHO Grade ≥3 during radiation therapy to the first WHO Grade 2 or lower OM Grade. Overall Duration of SOM was defined as the number of days from initial WHO Grade ≥3 during radiation therapy to the day prior to the next OM assessment after the last WHO Grade ≥3 during/after radiation therapy. Note: 50th percentiles are from Kaplan-Meier analysis. Patients who did not experience SOM have duration set to 0.

Previously, the Company reported statistically significant results showing Brilacidin-OM reduced the incidence of SOM in HNC patients receiving cisplatin administered in a high-dose regimen (80-100 mg/m2), approximately every 21 days. For the Modified Intent-to-Treat (mITT) population, Brilacidin-OM in the high-dose chemotherapy regimen reduced the incidence of SOM by 65.0% ([incidence control- incidence active]/incidence control) as compared with placebo (Brilacidin: 25.0%; placebo: 71.4%; p=0.0480). For the Per Protocol (PP) population, Brilacidin-OM in the high-dose chemotherapy regimen similarly reduced the incidence of SOM by 80.3% as compared with placebo (Brilacidin: 14.3%; placebo: 72.7%; p=0.0249).

Exploratory Endpoint: Unplanned Office Visits, Emergency Department Visits, and/or Hospital Admissions Due to OM

Positive OM assessment endpoints are additionally supported by zero (0) of the patients in the Brilacidin-OM group having unplanned office visits, ED visits, or hospital admissions due to OM, compared to four (4) patients in the placebo group.

Other Study Observations

Regardless of the oral sites irradiated (at least two sites from: buccal mucosa, floor of mouth, ventral/lateral tongue, and soft palate), the incidence by patient of Severe OM on Brilacidin-OM relative to placebo was consistently reduced.

Across cumulative radiation dose intervals, patients in the Brilacidin-OM group consistently reported less often feeling the sensation "swollen" (approximately half of that reported for the placebo group). "Burning" sensation also was reported consistently less frequently in the Brilacidin treatment group.

Patients in the Brilacidin-OM group appeared to trend more favorably over the course of chemoradiation treatment according to Eastern Cooperative Oncology Group (ECOG) Performance Status—a common set of criteria used in oncology trials to assess debility.

Management Comments

"Drug makers, the world-over, have spent decades and enormous sums in both money and resources trying to develop an effective OM drug in a bid to address dire patient needs as well as capture a tremendous market opportunity," commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "Yet, there is currently no drug approved to treat, let alone prevent, severe OM in patients with Head and Neck Cancer. Most Pharmas currently conducting OM trials target shortening the duration of severe OM as their primary endpoint, not reduction of incidence, like we did. The Brilacidin-OM Phase 2 trial met its primary objective and its key secondary objectives. As we continue to analyze subset data, we are extremely enthusiastic about observed trends. Hundreds of thousands of patients would benefit from a preventative OM treatment and we’re excited that Brilacidin-OM may one day provide these patients a much-needed breakthrough treatment option."

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On April 16, 2018 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that the Company’s randomized, Phase 2b METRIC Study of glembatumumab vedotin compared to Xeloda (capecitabine) in patients with metastatic triple-negative breast cancers that overexpress gpNMB failed to meet its primary endpoint, progression-free survival (PFS) as assessed by an independent, central reading of patient scans (Hazard ratio = 0.95; median PFS: glembatumumab vedotin 2.9 months vs. Xeloda 2.8 months; p=0.76) (Press release, Celldex Therapeutics,APR 16, 2018, View Source [SID1234525681]). There was no significant advantage for glembatumumab vedotin in key secondary endpoints, including overall response rate, duration of response and overall survival. The glembatumumab vedotin safety profile was consistent with prior experience.

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"Triple-negative breast cancer is a very difficult disease to treat, and we are extremely disappointed for patients that the METRIC Study was not successful," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "On behalf of Celldex, I want to express our gratitude to the METRIC investigators, patients and families who participated in this study. Based on these results, we have also made the decision to discontinue the glembatumumab vedotin program across all indications and are currently prioritizing our pipeline, which includes five candidates in ongoing clinical studies. In line with this, we are evaluating our operational and workforce needs to extend our financial resources and direct them to continued pipeline advancement. Once we solidify these plans, we intend to update investors."

Celldex’s clinical-stage pipeline includes the following compounds:

Varlilumab, a CD27 agonist, currently completing a Phase 2 study in combination with Opdivo in multiple indications with data expected to be presented at multiple medical meetings in 2018;
CDX-3379, an ErbB3 inhibitor, which is expected to complete enrollment in the first stage of a Phase 2 study in combination with Erbitux in head and neck cancer during the third quarter of 2018;
CDX-014, a TIM-1 targeted agent, which is actively enrolling patients in a Phase 1 study in renal cell and ovarian clear cell carcinomas;
CDX-1140, a CD40 agonist, which is actively enrolling patients in a Phase 1 study in various solid tumors; and,
CDX-301, a dendritic cell mobilizer, currently being studied in an investigator-sponsored study in combination with radiation therapy in advanced non-small cell lung cancer. Data from this study were presented in a plenary session at the AACR (Free AACR Whitepaper) Annual Meeting on Sunday, April 15, 2018.
Celldex believes its pipeline prioritization and organizational restructuring efforts will extend financial resources beyond the guidance issued in the Company’s year-end 2017 earnings press release and associated filings. The Company plans to provide revised guidance in its first quarter 2018 financial results in early May.

Webcast and Conference Call
Celldex executives will host a conference call at 8:00 a.m. ET today to discuss topline METRIC results. The conference call will be webcast live over the internet and can be accessed by going to the "Events & Presentations" page under the "Investors & Media" section of the Celldex Therapeutics website at www.celldex.com. The call can also be accessed by dialing (866) 743-9666 (within the United States) or (760) 298-5103 (outside the United States). The passcode is 7786951.

A replay of the call will be available approximately two hours after the live call concludes through April 23, 2018. To access the replay, dial (855) 859-2056 (within the United States) or (404) 537-3406 (outside the United States). The passcode is 7786951. The webcast will also be archived on the Company’s website.

About METRIC
The METRIC study is a randomized Phase 2b study of glembatumumab vedotin in patients with metastatic triple-negative breast cancers that overexpress gpNMB. In this indication, overexpression is defined as greater than or equal to 25% of tumor cells testing positive for gpNMB. Patients were randomized 2 to 1 to either glembatumumab vedotin or to capecitabine, also known by the tradename Xeloda, as a comparator. In total, 327 patients were enrolled into METRIC. The primary endpoint of the study is progression-free survival (PFS), which is defined as the time from randomization to the earlier of disease progression, assessed based on an independent, central reading of patient scans, or death due to any cause. The study called for 203 progression events for evaluation of the primary endpoint. The sum of the data, including the secondary endpoints of response rate, overall survival, duration of response and safety, are also important in assessing clinical benefit.

About Glembatumumab Vedotin
Glembatumumab vedotin is a fully human monoclonal antibody-drug conjugate (ADC) that targets glycoprotein NMB (gpNMB). gpNMB is a protein overexpressed by multiple tumor types, including breast cancer, melanoma, lung cancer, uveal melanoma and osteosarcoma. The gpNMB-targeting antibody, CR011, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. Glembatumumab vedotin is designed to be stable in the bloodstream but to release MMAE upon internalization into gpNMB-expressing tumor cells, resulting in a targeted cell-killing effect.

Xeloda is a registered trademark of Genentech, Inc. Opdivo is a registered trademark of Bristol-Myers Squibb. Erbitux is a registered trademark of Eli Lilly & Co.

On 16 April 2018 Crescendo Biologics Ltd (Crescendo), the developer of multifunctional biologics, including targeted T-cell engagers, reported that it has achieved the first major technical milestone under the terms of its collaboration with Takeda Pharmaceutical Company Limited (Takeda; TSE: 4502) (Press release, Crescendo Biologics, APR 16, 2018, View Source [SID1234525320]).
The global, strategic, multi-target collaboration and license agreement with Takeda was announced in October 2016. Under this agreement, Crescendo’s proprietary transgenic platform and engineering expertise is being used to identify and optimally configure Humabody-based therapeutics against targets selected by Takeda.

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This milestone, for an undisclosed amount, marks the successful delivery of a highly diverse panel of Humabody leads, directed to the first of Takeda’s selected targets.
Dr Peter Pack, CEO of Crescendo, commented:
"This milestone is an important step forward in our relationship with Takeda. It demonstrates our ability to deliver a diverse selection of characterised Humabody molecules that meet the stringent specifications outlined in the agreement. In conjunction with Takeda’s deep expertise in the field of oncology, this exciting milestone provides further validation of Crescendo’s ability to create optimally configured Humabodies.
"This milestone demonstrates the potential of this innovative technology and brings us closer to our goal of developing next generation, highly modular and targeted biologics against cancer."