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Bellicum Pharmaceuticals Announces Submission of BPX-701 and BPX-601 Clinical Trial Protocols for Review by the NIH RAC

On January 11, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported regulatory milestones and program updates on its CAR T and TCR product candidates (Press release, Bellicum Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508738]).

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Bellicum is preparing for the initiation of clinical studies in 2016 of its three most advanced CAR T and TCR adoptive cell therapy product candidates, BPX-701, BPX-601, and BPX-401. Today the Company submitted required documentation, including clinical trial protocols, for BPX-701 and BPX-601 for review by the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC). If selected for public review, such review would be expected to take place at the next RAC meeting scheduled for March 8-10, 2016.

The Company further announced that it expects to begin enrolling patients in Phase 1 trials of BPX-701 and BPX-601 in mid-2016, and BPX-401 in the second half of 2016, with IND filings to follow RAC review in each case.

BPX-701 is a CaspaCIDe-enabled natural high affinity T cell receptor (TCR) product candidate designed to target malignant cells expressing the preferentially-expressed antigen in melanoma (PRAME). Initial planned indications for BPX-701 development are Refractory or Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) with an additional study planned for metastatic uveal melanoma. Each of these are orphan indications where PRAME is highly expressed and for which current treatment options are limited. The Company expects to submit European regulatory filings to allow initiation of clinical development at a European site after the U.S. IND has been allowed.

BPX-601 is a GoCAR-T product candidate containing Bellicum’s proprietary iMC (inducible MyD88/CD40) activation switch, designed to treat solid tumors expressing prostate stem cell antigen (PSCA). As reported at ASH (Free ASH Whitepaper), preclinical data shows enhanced T-cell proliferation, persistence and in vivo anti-tumor activity compared to traditional CAR T therapies. The initial planned indication for BPX-601 development is non-resectable pancreatic cancer.

BPX-401 is a CIDeCAR product candidate incorporating Bellicum’s proprietary MC co-stimulatory domain and the CaspaCIDe safety switch, designed to target blood cancers expressing CD19.

"Throughout 2015, we made significant progress across all of our adoptive cell therapy programs," said Tom Farrell, President and CEO of Bellicum Pharmaceuticals. "We’re now poised to bring three novel CAR T and TCR product candidates into the clinic in 2016, utilizing our molecular switch and proprietary co-stimulatory domain technologies. Importantly, we have in place the financial and management resources needed not only to bring these novel programs forward but also to continue discovering exciting new ways that our technologies can potentially improve the treatment of cancers and other diseases."

Background on the NIH RAC Process

Clinical trial protocols and other required information for product candidates that involve gene transfer are reviewed by both the FDA and the NIH, through the Recombinant DNA Advisory Committee or RAC. The NIH’s Office of Biotechnology Activities (OBA) convenes quarterly RAC meetings to make recommendations and selectively elicit public discussion of scientific, safety or ethical issues. The OBA notifies the FDA of the outcome of RAC reviews and reports are posted to the OBA website.

Agios Outlines Key 2016 Goals and Priorities

On January 11, 2016 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the company’s 2016 strategy and expected clinical development and research milestones in conjunction with the 34th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508737]). The presentation will outline three strategic priorities for 2016: continue rapid and broad late-stage clinical development for its lead isocitrate dehydrogenase (IDH) mutant inhibitors in hematologic malignancies and solid tumors; demonstrate clinical activity of its wholly owned, global pyruvate kinase-R (PKR) activators in patients; and advance research and initiate preclinical development of a program from the next wave of research.

"We expect each of our programs to achieve important catalysts in 2016 that will bring us closer to our vision of helping people with cancer and rare genetic disorders," said David Schenkein, M.D., chief executive officer at Agios. "We believe these milestones, coupled with our growing late-stage development and commercial capabilities, set Agios firmly on the path to become a sustainable, multi-product biopharmaceutical company with a strong research core and broad pipeline of first-in-class medicines."

IDH Mutant Inhibitors

Dr. Schenkein continued, "We remain focused on executing on our ‘speed and breadth’ clinical development strategy for AG-221 and AG-120 in hematological malignancies, with the intent to complete enrollment of both 125-patient expansion cohorts this year. Further understanding the potential of our IDH mutant inhibitors in solid tumors remains a priority with several new and ongoing trials in 2016."

AG-221, AG-120 and AG-881 are part of Agios’ global strategic collaboration with Celgene Corporation.

Expected 2016 milestones for IDH mutant inhibitors in hematologic malignancies:

Complete enrollment of both 125-patient expansion cohorts for the Phase 1/2 study of AG-221 and Phase 1 study of AG-120 in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in the second half of 2016
Initiate a global, registration-enabling Phase 3 study of AG-120 in frontline AML patients with an IDH1 mutation in the second half of 2016

Initiate an expansion arm in high-risk myelodysplastic syndrome patients for AG-221 in 2016
Initiate a Phase 1/2 frontline combination study of AG-221 or AG-120 with VIDAZA (azacitidine) in newly diagnosed AML patients not eligible for intensive chemotherapy in the first quarter of 2016

Continue to enroll patients in the following ongoing clinical trials:
Phase 3 IDHENTIFY study of AG-221 vs. standard of care chemotherapy in R/R AML
Phase 1b frontline combination study of AG-221 or AG-120 with standard-of-care intensive chemotherapy in AML
Phase 1 dose-escalation and expansion study of AG-881 in IDH mutant positive hematologic malignancies

Expected 2016 milestones for IDH mutant inhibitors in solid tumors:

Initiate a randomized Phase 2 study of AG-120 in IDH1 mutant positive cholangiocarcinoma in the second half of 2016
Continue to enroll patients in the following ongoing clinical trials:

Expansion phase of the ongoing Phase 1 study of AG-120 in advanced IDH1 mutant positive solid tumors
Phase 1 dose-escalation and expansion study of AG-881 in IDH mutant positive solid tumors

PKR Activators

"Having initiated dosing in the Phase 1 healthy volunteer study of AG-519, we’ve completed the first of several key clinical milestones expected from our PKR activators in the first half of this year," said Dr. Schenkein. "Notably, we expect to present the first data from this study and the Phase 2 DRIVE PK study for AG-348 in PK deficiency patients. There are currently no approved or disease-modifying treatments for PK deficiency, which drives our focus on advancing potential new treatment options for these patients."

Milestone announced today:

Dosing was initiated in an integrated single ascending dose (SAD) and multiple ascending dose (MAD) placebo-controlled Phase 1 study of AG-519 in healthy volunteers

Expected 2016 milestones for PKR activators:

Present the first data from DRIVE PK, a global Phase 2, open-label safety and efficacy trial of AG-348 in adult, transfusion-independent patients with PK deficiency in the first half of 2016

Present data from Phase 1 study of AG-519 in healthy volunteers as well as preclinical findings about the molecule in the first half of 2016

Outline the clinical development plans for Agios’ PKR activators in beta-thalassemia in the second half of 2016

Present new findings from the Natural History Study of PK deficiency being conducted with Boston Children’s Hospital in the second half of 2016

Research Programs

"We continue to focus on discovering and validating first-in-class targets that meet our high bar for development and align with our precision medicine strategy," said Scott Biller, Ph.D., chief scientific officer at Agios. "We are excited to move the first program in our next wave of investigational medicines into preclinical development this year."

Agios scientists have discovered a novel pathway comprised of multiple targets with a shared vulnerability in MTAP-deleted tumors and have demonstrated that this pathway can be modulated by small molecule inhibitors, resulting in robust anti-tumor activity in animal models
MTAP (methylthioadenosine phosphorylase) is a metabolic enzyme that is deleted in approximately 15 percent of all cancers. This deletion is readily detected by a simple genomic test, thus allowing the selection of patients predicted to be sensitive to the therapy.

Expected 2016 milestones for research:

Publish preclinical findings on a new cancer metabolism program
Initiate preclinical development activities for the first molecule in the next wave of novel investigational medicines
Presentation at 34th Annual J.P. Morgan Healthcare Conference
Agios will webcast its corporate presentation from the 34th Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 11, 2016 at 3:30 p.m. PST (6:30 p.m. EST). A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.

AstraZeneca and Moderna Therapeutics announce new collaboration to co-develop and co-commercialise immuno-oncology mRNA therapeutics™

On January 11, 2016 AstraZeneca, along with its global biologics research and development arm, MedImmune, and Moderna Therapeutics reported a new collaboration to discover, co-develop and co-commercialise messenger RNA (mRNA) therapeutic candidates for the treatment of a range of cancers (Press release, AstraZeneca, JAN 11, 2016, View Source [SID:1234508734]). The collaboration is in addition to the agreement announced by the companies in 2013 to develop mRNA Therapeutics for the treatment of cardiovascular, metabolic and renal diseases as well as selected targets in oncology.

The collaboration will combine MedImmune’s protein engineering and cancer biology expertise with Moderna’s mRNA platform. mRNA-based therapies are an innovative treatment approach that enables the body to produce therapeutic protein in vivo, opening up new treatment options for a wide range of diseases that cannot be addressed today using existing technologies.

Under the terms of the new agreement, AstraZeneca and Moderna, a pioneer of mRNA Therapeutics, have agreed to collaborate on two specific immuno-oncology programmes, based on promising pre-clinical data, including pharmacology in tumour models. Moderna will fund and be responsible for discovery and preclinical development of product candidates, with the aim of delivering one Investigational New Drug (IND) application-ready molecule for each of the two programmes. Moderna’s efforts will be led by its oncology-focused venture, Onkaido. AstraZeneca will be responsible for early clinical development, led by MedImmune, and Moderna and AstraZeneca will share the costs of late-stage clinical development. The two companies will co-commercialise resulting products in the US under a 50:50 profit sharing arrangement. AstraZeneca will lead ex-US commercialisation efforts, with Moderna receiving tiered royalties up to substantial double digits on ex-US sales.

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "We’re pleased to be expanding our relationship with Moderna with this new collaboration, to advance the potential of pioneering messenger RNA technology in developing game-changing new treatments for cancer patients."

"Since our companies’ original strategic agreement in March 2013, Moderna’s relationship with AstraZeneca has been very fruitful. This new agreement with AstraZeneca demonstrates the effectiveness of our existing relationship and the power of our mRNA technology," said Stéphane Bancel, Chief Executive Officer of Moderna. "We’re gratified to deepen our relationship with AstraZeneca and MedImmune with this major initiative, and we look forward to getting underway immediately with our new joint immuno-oncology programmes."

Under the companies’ original strategic agreement, AstraZeneca holds exclusive access to select any target of its choice in cardiometabolic diseases, as well as select targets in oncology, over a period of up to five years for subsequent development in mRNA. Several projects are progressing towards clinical development under the arrangement, and a first-in-human study is expected to commence in late 2016.

8-K – Current report

On January 11, 2016 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported an update on its evofosfamide program including that Threshold and Merck KGaA, Darmstadt, Germany have agreed upon key terms for the licensing back of all rights to evofosfamide to Threshold (Filing, 8-K, Threshold Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508731]). The companies have a global license and co-development agreement for evofosfamide, an investigational hypoxia-activated prodrug for the treatment of cancer, which was discovered and initially developed by Threshold.

The decision to return rights to evofosfamide to Threshold follows the unblinding of two Phase 3 clinical trials of evofosfamide (TH-CR-406 and MAESTRO) and a previously unplanned, subsequent interim futility analysis of a Phase 2 clinical trial of evofosfamide in patients with non-squamous non-small cell lung cancer (n-s NSCLC). As previously announced, both Phase 3 trials failed to meet the primary endpoint of demonstrating a statistically significant improvement in overall survival. The results of the MAESTRO trial will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Gastrointestinal Cancers Symposium during an oral presentation session scheduled to begin at 2:00 p.m. Pacific Time on Friday, January 22, 2016 (Abstract #193).

Following the topline results from the two Phase 3 clinical trials, Threshold and Merck KGaA, Darmstadt, Germany decided to unblind the Phase 2 clinical trial in n-s NSCLC and conduct an interim futility analysis. The Phase 2 trial was designed to enroll 440 patients with advanced n-s NSCLC. A total of 265 patients were enrolled and 112 events (deaths) were reported at the time of the interim analysis. An independent Data Safety Monitoring Board conducted the analysis and concluded that the trial is unlikely to reach its primary endpoint of improving overall survival with statistical significance. As a result, further enrollment in this trial will be closed. Additional findings from the interim analysis indicated that evofosfamide plus pemetrexed demonstrated longer progression-free survival (PFS) associated with a reduction in the risk of progression or death by approximately 30%. No new safety findings were reported. Data for this trial will be finalized and results presented at a future medical meeting.

"We are pleased to have agreed to key terms for the licensing back of all rights to evofosfamide to Threshold and we will share our plans for the future development of evofosfamide once our ongoing analyses of the data from the recently unblinded clinical trials are complete," said Barry Selick, Ph.D., Chief Executive Officer of Threshold. "In parallel, we continue to focus on prosecuting two Phase 2 clinical trials of tarloxotinib, our hypoxia-activated EGFR tyrosine kinase inhibitor, and to assess other strategic options for the company."

About Evofosfamide

Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Threshold previously announced the outcomes of two Phase 3 studies (MAESTRO and TH-CR-406/SARC021) of evofosfamide stating that neither study met its primary endpoint. The related news release dated December 7, 2015, can be accessed on the company’s website in the Investors/News Releases section View Source

About Tarloxotinib Bromide

Tarloxotinib bromide (the proposed International Nonproprietary Name), or "tarloxotinib", is a prodrug designed to selectively release a covalent (irreversible) EGFR tyrosine kinase inhibitor under severe hypoxia, a feature of many solid tumors. Accordingly, tarloxotinib has the potential to effectively shut down aberrant EGFR signaling in a tumor-selective manner, thus potentially avoiding or reducing the systemic side effects associated with currently available EGFR tyrosine kinase inhibitors. Tarloxotinib is currently being evaluated in two Phase 2 proof-of-concept trials: one for the treatment of patients with mutant EGFR-positive, T790M-negative advanced non-small cell lung cancer progressing on an EGFR tyrosine kinase inhibitor, and the other for patients with recurrent or metastatic squamous cell carcinomas of the head and neck or skin. Threshold licensed exclusive worldwide rights to tarloxotinib from the University of Auckland, New Zealand, in September 2014.

8-K – Current report

On January 11, 2016 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology and Servier Canada Inc., an affiliate of Servier a research-oriented pharmaceutical company which is pioneering new therapies primarily for cancer and cardiovascular diseases, reported the signing of a strategic partnership (Filing, 8-K, Spectrum Pharmaceuticals, JAN 11, 2016, View Source [SID:1234508730]).

As part of this partnership, Spectrum will grant the exclusive rights to develop and commercialize in Canada a franchise of four Spectrum hemato-oncology drugs: Zevalin (ibritumomab tiuxetan) Injection for intravenous use, Folotyn(pralatrexate injection), Beleodaq (belinostat) for Injection and Marqibo (vinCRIStine sulfate LIPOSOME injection) for intravenous infusion. Spectrum will receive $6 million in upfront payments, plus development milestone payments and royalties based on net product sales.

"We are pleased to announce this strategic partnership with Servier, a leading company in Canada," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "This deal allows us to continue to focus on our core priorities including SPI-2012, Poziotinib, Apaziquone and Evomela. This year we plan to initiate two key trials with drugs that target blockbuster markets and we are looking forward to hearing from the FDA on two of our NDA submissions. We believe that our pipeline has never been as strong as it is today, and we continue to focus on executing on our key priorities."

"This strategic partnership between Spectrum Pharmaceuticals and Servier Canada will contribute to consolidate our global strategy in Oncology. Our ambition is to become a benchmark player in this field," said Frédéric Sesini, Executive Vice-President International Operations of Groupe Servier. "We are fully committed in providing Canadian patients with innovative treatment options. With this key partnership, Servier Canada Oncology will start operating and will work to make these treatments available soon," underlined Frederic Fasano, Chief Executive Officer of Servier Canada Inc.