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Termination of Phase I, open-label, dose finding study (NCT02641002) of CC-90002 in subjects with acute myeloid leukemia and high-risk myelodsplastic syndrome

A Phase I, open-label, dose finding study (NCT02641002) of CC-90002 in subjects with acute myeloid leukemia and high-risk myelodsplastic syndrome has been terminated due to that preliminary monotherapy data in relapsed/refractory AML and high-risk MDS did not offer a sufficiently encouraging profile for further dose escalation/expansion (Clinical trial, ClinicalTrials.gov, OCT 4, 2018, View Source;B=13&C=merged#StudyPageTop [SID1234531854]).

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However another Phase I, open-label, dose finding study (NCT02367196) of CC-90002 in subjects with advanced solid and hematologic cancers is still active and confirmed by Celgene October 16, 2018 (Clinicaltrials.gov, OCT 16, 2018, View Source).

Celyad Announces Exclusive Agreement for
Horizon Discovery’s shRNA Platform to Develop Next-Generation Allogeneic CAR-T Therapies

On October 4, 2018 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell-based therapies, reported an exclusive agreement with Horizon Discovery Group plc (LSE: HZD), for the use of its shRNA technology to generate Celyad’s second non-gene-edited allogeneic platform (Press release, Celyad, OCT 4, 2018, View Source [SID1234530340]).

Celyad recently announced its first-in-class non-gene edited allogeneic CAR-T candidate, CYAD-101 a non-gene-edited allogeneic NKG2D-based CAR using the TIM (TCR Inhibiting Molecule). As a result of the agreement with Horizon Discovery, Celyad now also has access to a novel shRNA-based platform.

Data from preclinical studies demonstrating the versatility of the shRNA platform in the allogeneic setting, will be presented at the upcoming 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington, D.C., November 7th – 11th. These promising preclinical data will pave the way for the next steps in the development of Celyad’s differentiated non-gene edited allogeneic approach to CAR-T cell therapy.

"We are excited to have the opportunity to leverage Horizon’s shRNA platform to further advance our pioneering approach to non-gene edited allogeneic CAR-T cells", said Dr. Christian Homsy, CEO of Celyad. "Celyad is committed to rapidly advancing its allogeneic program based on highly promising preclinical data which will be presented at SITC (Free SITC Whitepaper). These data provide proof of concept for our shRNA based non-gene-edited allogeneic approach. In addition to very promising preclinical data, our allogeneic approach is also strengthened by Celyad’s strong patent estate in the U.S., which broadly covers the use of allogeneic CAR-T using cells that are TCR inhibited or suppressed by any means."

Jon Moore, CSO of Horizon Discovery added: "The high performance shRNA technology licensed by Celyad is the same as that deployed in our range of SMARTvector products and is designed to deliver efficient target knock down with high specificity. Horizon’s collaboration with Celyad is designed to let Celyad find a highly effective solution for its needs. Horizon sees its shRNA technology as a serious rival to gene editing approaches for delivering enhanced performance to therapeutic cell products. We see enormous promise in cell therapies and are committed to develop and supply innovative technologies that allow our partners to bring transformative cell therapies to the clinic and fulfil unmet clinical needs."

Pfizer to Award More Than $3 Million in Grants to Further Breast Cancer Research

On October 4, 2018 Pfizer Inc. reported the recipients of the Advancing Science through Pfizer Investigator Research Exchange (ASPIRE) Breast Cancer Research Awards (Press release, Pfizer, OCT 4, 2018, View Source [SID1234529942]). Four grants totaling more than $3 million (USD) in funding will be awarded to investigators in the United States (U.S.) to support clinical research projects involving Pfizer compounds in breast cancer. Since 2015, Pfizer has provided more than $16 million in total funding for the ASPIRE Oncology Research Awards Program across breast and hematologic cancers.

"The ASPIRE awards underscore Pfizer’s commitment to collaborating with investigators to expand scientific knowledge and improve the treatment of breast cancer," said Lynn McRoy, M.D., breast cancer lead, U.S. Medical Affairs, Pfizer Oncology. "The recipients of the 2018 awards submitted outstanding clinical research proposals that have the potential to advance care for people living with breast cancer."

Recipients of the 2018 awards were selected through a competitive application process overseen by an independent review panel of experts. The following investigators and studies have been selected to receive grants:

Dr. Mylin A. Torres, Glenn Family Breast Center, Winship Cancer Institute, Emory University – A Phase 2 Multi-institutional Study of Concurrent Radiotherapy, Palbociclib, and Hormone Therapy for Treatment of Bone Metastasis in Breast Cancer Patients
Dr. Aditya Bardia, Massachusetts General Hospital Cancer Center – Evaluation of Talazoparib, a PARP Inhibitor, for Patients With Somatic BRCA Mutant Metastatic Breast Cancer in a Genotyping Based Clinical Trial
Dr. Antoinette Tan, Levine Cancer Institute, Atrium Health – IGNITE-Immunoprofiling of Gedatolisib, a Dual PI3-Kinase and mTOR Inhibitor, in the Neo-Immunoadjuvant Treatment of Early Stage Breast Cancer
Dr. Kari Wisinski, University of Wisconsin Carbone Cancer Center – Phase 2 Trial with Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1 or 2 Positive, HER2 Negative Breast Cancers
Investigators in the U.S. were encouraged to submit proposals for the 2018 ASPIRE Breast Cancer Research Awards that advance knowledge in the treatment and disease management of breast cancer. Proposals were eligible for IBRANCE (palbociclib), an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, for metastatic breast cancer, the most advanced stage of breast cancer (stage IV)1,2; talazoparib, an investigational, once-daily, oral poly ADP ribose polymerase (PARP) inhibitor; and gedatolisib (PF-05212384), an investigational, small molecule, dual inhibitor targeting the phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathways in the development of solid tumors.

For more information about ASPIRE, please visit www.aspireresearch.org.

About IBRANCE (palbociclib) 125 mg capsules
IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase
inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine
therapy.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

Heat Biologics’ Pelican Subsidiary Provides Update on its Novel PTX-35 T-Cell Costimulator

On October 4, 2018 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, and its Pelican Therapeutics subsidiary ("Pelican") reported updates its novel PTX-35 co-stimulatory antibody (Press release, Heat Biologics, OCT 4, 2018, View Source [SID1234529923]). PTX-35 is designed to harness the body’s natural antigen-specific immune activation mechanisms. When combined with immunotherapies, including checkpoint inhibitors as well as Heat’s ImPACT and ComPACT technologies, PTX-35 has been shown to enhance antigen-specific T-cell activation to eliminate tumor cells in pre-clinical models.

Recent PTX-35 highlights:

Completed cell line development and creation of validated master cell bank for cGMP manufacturing
Established CMC path for the production of GMP clinical material and non-clinical preliminary pharmacology / non-GLP toxicology studies
Preliminary non-GLP pharmacology demonstrates positive results, including efficient binding and activation on cells expressing the TNFRSF25 receptor, as well as increased expansion of T-cells in-vivo
2-week IND enabling dose range finding toxicology studies in primates receiving two doses show no signs or signals of clinical toxicity across wide dose range
Ongoing pre-IND discussions with FDA; expect to submit IND in Q1 2019
Rahul Jasuja, Ph.D., CEO of Pelican, commented, "We are progressing rapidly with our pre-clinical activities and expect to submit an IND for PTX-35 in the first quarter of 2019. We are strongly encouraged by the preliminary pre-clinical efficacy and safety data which shows no signs of toxicity across a wide range of doses."

Dr. Jasuja continued, "We have been efficient in our use of funds, which has allowed us to come in under budget, further extending our runway for this program. Given our operating efficiency thus far, we expect to receive the next tranche of grant funding once we fully utilize the funds that the Cancer Prevention Research Institute of Texas ("CPRIT") has previously provided. As we progress, our plan is to advance a broad clinical development program that could include combination therapy with Heat’s ImPACT and ComPACT therapies, as well as other costimulatory agonists, checkpoint inhibitors and immune modifiers to address the unmet need for patients who do not respond well to current cancer therapies."

The Company further reported that PTX-35 was featured in Nature’s Biopharma Dealmakers September 2018 edition, which is available at: View Source

To-date, Pelican has received $8.3 million in grants from CPRIT. The CPRIT award supports pre-clinical development, manufacturing and clinical development through a comprehensive 70-patient Phase 1 clinical trial for PTX-35. The Company expects to meet the qualifications to receive the third tranche of its $15.2 million CPRIT grant award, totaling $6.9 million, later this year.

Nimbus Therapeutics Names Jeb Keiper as President and Chief Executive Officer

On October 4, 2018 Nimbus Therapeutics, a biotechnology company applying deep computational chemistry expertise throughout drug discovery and development, reported that it has named Jeb Keiper, M.S., M.B.A., President and Chief Executive Officer, effective immediately (Press release, Nimbus Therapeutics, OCT 4, 2018, View Source [SID1234529887]). Mr. Keiper succeeds Donald Nicholson, Ph.D., and will lead the company forward as it progresses multiple programs toward clinical development.

"After over four years of building Nimbus and this exceptional team, the company is now poised to start the next chapter of developing important medicines for patients with autoimmune disease, cancer, and metabolic diseases," said Donald Nicholson, Ph.D. "In its next phase of growth, Nimbus will be led by a CEO with intimate knowledge of the company and a track record of successful leadership. Jeb’s deep business expertise and leadership experience made him an ideal partner to me and a logical successor. I am very much looking forward to starting the next entrepreneurial chapter of my career, and I am confident that Nimbus, the science and our employees are in great hands."

Mr. Keiper joined Nimbus in 2014 and initially served as Nimbus’ Chief Business Officer, and along with Dr. Nicholson, set the strategic direction of the company. In the ensuing four years, Nimbus brought in over $775 million of partnership and financing into the company, including the Series B financing in March 2015, the sale of Nimbus’ clinical NASH program to Gilead in May 2016 for $400 million upfront, the strategic immunology alliance with Celgene announced in October 2017, and a round of private expansion capital in 2018. Mr. Keiper was also appointed Chief Financial Officer in 2017.

Prior to Nimbus, Mr. Keiper was VP of Business Development at GSK Oncology and spent a decade at GlaxoSmithKline in various BD leadership roles. He led the oncology portion of the $16 billion GSK-Novartis transaction announced in April 2014. In 20 years of industry experience, starting as a bench chemist at Pfizer R&D and working in various roles from consulting at McKinsey to business development at TransForm Pharmaceuticals, Mr. Keiper has a track record of leading teams of talented scientists and managers to achieve stretch objectives, including advancing new medicines into clinical development, filing NDAs, and constructing transformative deals and financings.

"Jeb has been a critical component of the success at Nimbus over the last four years, and we are confident that he will lead the company into the future and its continued successful development of the pipeline," said Nimbus’ Chairman and co-founder Bruce Booth, D.Phil. "We thank Don for his passion and leadership in driving the accomplishments Nimbus has achieved to date and have immense respect for him as a scientist and a leader. I look forward to working with him on future innovative opportunities."

"Nimbus has pioneered new ways of discovering and developing important medicines for patients leveraging a globally distributed, virtually-enabled operating model," said Mr. Keiper. "Our success has challenged and reformed decades-old dogma on how to develop new small molecule medicines, and has been reflected in our partnerships with Gilead, Celgene, and Genentech. As we enter the next chapter, our ambition and business strategy remain the same: to continue innovating with computational methodologies for creating and advancing new medicines, and to couple those with cutting-edge discoveries in the mechanistic underpinnings of human disease."