Oncoceutics Expands Patent Family to Include Composition of Matter for ONC206 in Europe
Philadelphia, PA (March 4, 2019) – Oncoceutics, Inc. announced that the European Patent Office (EPO) has issued EP 3,068,401 entitled “7-benzyl-4-(2-methylbenzyl)-2,4,6,7,8,9-hexahydroimidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one, Salts Thereof and Methods of Use” with an expiration date of September 12, 2034. This patent covers the composition of matter for ONC206, its di-salt formulation, and its use in the treatment of cancer.
ONC206, a member of the imipridone family of anti-cancer small molecules, has demonstrated anti-cancer activity and safety in preclinical models and is planned to enter the clinic in 2019. These patents pave the path for the next generation of imipridones to enter the clinic and eventually the market.
This patent is the second issued on ONC206, following the composition of matter patent issued by the US Patent Office on June 28th, 2016, and greatly expands the company’s global IP protection.
“We are pleased that the European Patent Office has recognized ONC206 as an exciting novel invention and granted the appropriate patent protections,” said Martin Stogniew, Ph.D., Chief Development Officer of Oncoceutics. “The company’s current patent portfolio provides Oncoceutics with the opportunity to continue imipridone development and eventually provide ONC206 to European patients.”
Oncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds, i.e. the “imipridones,” that selectively target G protein-coupled receptors for oncology. The first lead compound to emerge from this program is ONC201, an orally active small molecule DRD2 antagonist. The company is supported by grants from NCI, FDA, Musella Foundation, XCures, Cancer Commons, and a series of private and public partnerships.
Visit Oncoceutics for more information.
Kymera Therapeutics to Present New Preclinical Data for its First-In-Class Oral IRAK4 Degrader in MYD88-Mutant Lymphoma at Late-Breaking Session of the American Association for Cancer Research Annual Meeting
Cambridge, Mass. (March 29, 2019) - Kymera Therapeutics Inc., a biotechnology company pioneering
targeted protein degradation to create breakthrough medicines for patients, will present new preclinical data for its first-in-class oral IRAK4 protein degrader, KYM-001, in MYD88-mutant lymphoma. Data will be presented in a late-breaking research session at the American Association for Cancer Research
Annual Meeting on April 3 from 8 a.m. – 12 p.m. (Poster #18, Session: Experimental and Molecular Therapeutics 2). The study showed that KYM-001 led to highly selective degradation of IRAK4 and tumor regression upon oral dosing, both alone and in combination with BTK inhibition.
“IRAK4 degraders offer an entirely new therapeutic approach to treat MYD88-driven B cell lymphomas, which are often aggressive and have a poor prognosis,” said Nello Mainolfi, PhD, co-founder and Chief Scientific Officer, Kymera Therapeutics and study co-author. “IRAK4 kinase and scaffolding functions are critical to MYD88-driven Myddosome signaling. Unlike conventional kinase inhibitors, our novel degrader KYM-001 removes both the kinase and scaffolding function of IRAK4 to effectively block Myddosome signaling, resulting in tumor growth arrest and subsequent regression. The team has been able to very quickly identify orally active degraders that offer ease and flexibility of dosing. ”
MYD88-activating mutations occur in 30-40% of patients with activated B cell-like (ABC) diffuse large B cell lymphoma (DLBCL). This study assessed the antitumor activity of Kymera’s orally active small molecule degraders in human ABC DLCBL cell lines in vitro and in tumor xenograft models in vivo, alone
and in combination with the BTK inhibitor ibrutinib.
Study Highlights “KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL alone and in combination with BTK inhibition”:
• KYM-001 induced potent and selective E3 ligase-dependent degradation of IRAK4 in multiple cellular models, resulting in 90% degradation at concentrations less than 100 nM.
• KYM-001 induced comparable levels of IRAK4 degradation in both MYD88 mutant and MYD88 WT human ABC DLBCL cell lines.
• KYM-001 impacted viability in MYD88 mutant, but not WT, ABC DLBCL cell lines, inducing apoptotic effects within 72 hours.
• Oral dosing of KYM-001 showed dose-dependent antitumor activity against the MYD88 L265P mutant ABC DLBCL cell line OCI-LY10, with >80% degradation of IRAK4 correlating with tumor regression in xenograft-bearing mice.
• KYM-001 was synergistic with the BTK inhibitor ibrutinib in vitro in ABC DLBCL cell lines bearing both MYD88 L265P and CD79 mutations. In vivo, this combined activity resulted in tumor regression at concentrations that were sub-optimal in single-agent studies, supporting further exploration of combinations that target oncogenic NFκB signaling.
About Kymera Therapeutics
Kymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by PegasusTM, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, www.kymeratx.com.
PegasusTM is Kymera Therapeutics’ proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities and degradation tools.
Verge Scientific Communications
New York, NY, June 28, 2019 – Pfizer Inc. (NYSE: PFE) today announced the United States (U.S.) Food and Drug Administration(FDA) has approved ZIRABEV™ (bevacizumab-bvzr), a biosimilar to Avastin® (bevacizumab),[i] for the treatment of five types of cancer: metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.[ii]
“Biosimilars like ZIRABEV can help increase access to impactful therapies, driving market competition that may ultimately lower costs and help address the diverse needs of patients living with cancer,” said Andy Schmeltz, Global President, Pfizer Oncology. “We are proud to add ZIRABEV to our growing oncology portfolio for U.S. patients living with a wide variety of tumor types.”
The FDA approval was based on review of a comprehensive data package which demonstrated biosimilarity of ZIRABEV to the reference product. This includes results from the REFLECTIONS B7391003 clinical comparative study, which showed clinical equivalence and found no clinically meaningful differences between ZIRABEV and the reference product in patients with advanced non-squamous NSCLC.[iii]
“ZIRABEV represents a welcome addition to the treatment armamentarium in its approved indications, potentially providing physicians with a medicine that has a similar safety profile and efficacy as the reference product,” said Dr. Niels Reinmuth, Department of Thoracic Oncology, Asklepios Lung Clinic, Munich-Gauting, Germany and lead author of the REFLECTIONS B7391003 study.[iv] “The FDA’s approval of ZIRABEV may provide an important new option for the treatment of multiple forms of cancer.”
Biosimilars have been a significant catalyst for change for the healthcare industry over the last decade, with the potential to create a more sustainable healthcare system. With more than 10 years of global in-market experience and six approved biosimilar products in the U.S., Pfizer is proud to be a leader and at the forefront of this vital healthcare segment. ZIRABEV is Pfizer’s second oncology monoclonal antibody (mAb) biosimilar to be approved by the FDA, following the FDA approval of TRAZIMERA™ (trastuzumab-qyyp) in March 2019.[v]ZIRABEV was also approved for use in the European Union (EU) in February 2019 for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent NSCLC, advanced and/or metastatic RCC and persistent, recurrent or metastatic carcinoma of the cervix.[vi]
About ZIRABEV (bevacizumab-bvzr)
ZIRABEV is a mAb biosimilar of the reference product, Avastin, which works by inhibiting the formation of new blood cells (angiogenesis) by specifically recognizing and binding to vascular endothelial growth factor (VEGF) protein. As part of the REFLECTIONS clinical trial program, ZIRABEV has been studied in nearly 400 patients to date.3,[vii],[viii],[ix]
ZIRABEV IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Gastrointestinal Perforations and Fistulae. Serious and sometimes fatal gastrointestinal perforation occurred at a higher incidence in patients receiving bevacizumab products compared to patients receiving chemotherapy. Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer). Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any internal organ
- Surgery and Wound Healing Complications. The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in bevacizumab-treated patients. Withhold for at least 28 days prior to elective surgery. Do not administer for at least 28 days following surgery and until the wound is fully healed. Discontinue in patients who develop wound healing complications that require medical intervention or necrotizing fasciitis
- Hemorrhage. Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding occurred up to 5-fold more frequently in patients receiving bevacizumab. In clinical studies, the incidence of grade ≥3 hemorrhagic events among patients receiving bevacizumab ranged from 0.4% to 7%. Do not administer ZIRABEV to patients with serious hemorrhage or a recent history of hemoptysis (≥1/2 tsp of red blood). Discontinue ZIRABEV in patients who develop grade 3–4 hemorrhage
- Additional serious and sometimes fatal adverse events with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
- Arterial thromboembolic events (grade ≥3, 5%, highest in patients with GBM). Discontinue in patients who develop a severe ATE.
- Renal injury and proteinuria. Monitor proteinuria during ZIRABEV therapy. Patients with a 2+ or greater urine dipstick reading should undergo 24-hour urine collection. Withhold for proteinuria >2 grams per 24 hours and resume when less than 2 grams per 24 hours. Discontinue in patients who develop nephrotic syndrome
- Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
- Nephrotic syndrome (<1%)
- Additional serious adverse events with increased incidence in the bevacizumab-treated arm vs chemotherapy arm included:
- Venous thromboembolism (grade ≥3, 11% seen in Study GOG-0240). Discontinue ZIRABEV in patients with a Grade 4 VTE, including pulmonary embolism
- Hypertension (grade 3–4, 5%–18%). Monitor blood pressure during treatment and, for ZIRABEV associated hypertension, continue monitoring after discontinuation. Withhold for severe hypertension. Discontinue for hypertensive crisis or hypertensive encephalopathy
- Posterior reversible encephalopathy syndrome (PRES) (<0.5%). Discontinue ZIRABEV in patients who develop PRES. Symptoms usually resolve or improve within days after discontinuing bevacizumab products, although some patients have experienced ongoing neurologic sequelae.
- Congestive heart failure (CHF) (1%). Discontinue ZIRABEV in patients who develop CHF
- Infusion-related reactions with the first dose of bevacizumab occurred in <3% of patients, and severe reactions occurred in 0.2% of patients. Decrease the rate of infusion for mild infusion-related reactions. Interrupt the infusion in patients with clinically significant infusion-related reactions and consider resuming at a slower rate following resolution. Discontinue in patients who develop a severe infusion-related reaction and administer appropriate medical therapy
- Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with ZIRABEV
- Based on the mechanism of action and animal studies, bevacizumab products may cause fetal harm
- Advise female patients that bevacizumab products may cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy
- Advise females of reproductive potential to use effective contraception during treatment with ZIRABEV and for 6 months after the last dose of ZIRABEV
- Advise nursing women that breastfeeding is not recommended during treatment with ZIRABEV and for 6 months following their last dose of treatment
- Bevacizumab products may impair fertility
Most Common Adverse Events
- Across studies, the most common adverse reactions observed in bevacizumab patients at a rate >10% were:
- Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis
- Across all studies, bevacizumab was discontinued in 8% to 22% of patients because of adverse reactions
Indication-Specific Adverse Events
- In first-line metastatic colorectal cancer (MCRC), the most common grade 3–4 events in Study 2107, which occurred at a (≥2%) higher incidence in the bevacizumab plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)
- In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the bevacizumab plus FOLFOX4 vs FOLFOX4 groups, were fatigue (19% vs 13%), diarrhea (18% vs 13%), sensory neuropathy (17% vs 9%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), hypertension (9% vs 2%), abdominal pain (8% vs 5%), hemorrhage (5% vs 1%), other neurological (5% vs 3%), ileus (4% vs 1%), and headache (3% vs 0%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study
- In non–small cell lung cancer (NSCLC), grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a (≥2%) higher incidence in bevacizumab-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thromboembolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)
- In recurrent glioblastoma (rGBM) Study EORTC 26101, 22% of patients discontinued treatment in the bevacizumab with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving bevacizumab with lomustine, the adverse reaction profile was similar to that observed in other approved indications
- In metastatic renal cell carcinoma (mRCC), the most common grade 3–5 adverse events in Study BO17705, occurring at a (≥2%) higher incidence in bevacizumab-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%, including hypertension and hypertensive crisis), and hemorrhage (3% vs 0.3%, including epistaxis, small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, hemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma)
- In persistent, recurrent, or metastatic cervical cancer, grade 3 or 4 adverse reactions in Study GOG-0240, occurring at a higher incidence (≥2%) in 218 patients receiving bevacizumab plus chemotherapy compared to 222 patients receiving chemotherapy alone, were abdominal pain (12% vs 10%), diarrhea (6% vs 3%), anal fistula (4% vs 0%), proctalgia (3% vs 0%), urinary tract infection (8% vs 6%), cellulitis (3% vs 0.5%), fatigue (14% vs 10%), hypertension (11% vs 0.5%), thrombosis (8% vs 3%), hypokalemia (7% vs 4%), hyponatremia (4% vs 1%), dehydration (4% vs 0.5%), neutropenia (8% vs 4%), lymphopenia (6% vs 3%), back pain (6% vs 3%), and pelvic pain (6% vs 1%)
Metastatic Colorectal Cancer
ZIRABEV, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with metastatic colorectal cancer (mCRC).
ZIRABEV, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product-containing regimen.
Limitation of Use: ZIRABEV is not indicated for adjuvant treatment of colon cancer.
First-Line Non-Squamous Non-Small Cell Lung Cancer
ZIRABEV, in combination with carboplatin and paclitaxel, is indicated for the first line treatment of patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer (NSCLC).
ZIRABEV is indicated for the treatment of recurrent glioblastoma (GBM) in adults.
Metastatic Renal Cell Carcinoma
ZIRABEV, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma (mRCC).
Persistent, Recurrent, or Metastatic Cervical Cancer
ZIRABEV, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.
Please see full Prescribing Information for ZIRABEV (bevacizumab-bvzr).
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 18 approved innovative cancer medicines and biosimilars across more than 20 indications, including breast, prostate, kidney, lung and hematology. Pfizer Oncology is striving to change the trajectory of cancer.
Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is as of June 28, 2019. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about ZIRABEV (bevacizumab-bvzr), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the launch timing and commercial success of ZIRABEV in the United States; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when applications for ZIRABEV may be filed in any other jurisdictions; whether and when any such other applications for ZIRABEV that may be pending or filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether ZIRABEV will be commercially successful; intellectual property and/or litigation implications;decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of ZIRABEV; uncertainties regarding access challenges for our biosimilar products where our product may not receive appropriate formulary access or remains in a disadvantaged position relative to the innovator product; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2018 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
[i] Avastin® is a registered trademark of Genentech Inc.
[ii] ZIRABEV™ (bevacizumab-bvzr) Prescribing Information. New York. NY: Pfizer Inc: 2019. Available at http://labeling.pfizer.com/ShowLabeling.aspx?id=11860.
[iii] Socinski MA, Von Pawel J, Kasahara K, et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced nonsquamous non-small cell lung cancer. Abstract 109. Presented at ASCO 2018.
[iv] American Cancer Society. Cancer Facts & Figures 2019. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed June 2019.
[v] TRAZIMERA™ (trastuzumab-qyyp) Prescribing Information. New York. NY: Pfizer Inc: 2019. Available athttps://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761081s000lbl.pdf. Accessed June 2019.
[vi] European Medicines Agency. Zirabev Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/zirabev-epar-product-information_en.pdf. Accessed June 2019.
[vii] Knight B, Rassam D, Liao S, et al. A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers. Cancer Chemother Pharmacol. 2016. 77:839-846.
[viii] Clinicaltrials.gov. NCT02031991. A pharmacokinetic study comparing PF-06439535 and bevacizumab in healthy male volunteers (REFLECTIONS B739-01). Available at https://clinicaltrials.gov/ct2/show/NCT02031991?term=reflections+bevacizumab&rank=1. Accessed June 2019.
[ix] Pfizer. Pfizer announces positive top-line results from the comparative REFLECTIONS B7391003 study for PF-06439535, a potential biosimilar to Avastin® (bevacizumab). Available at https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_positive_top_line_results_from_the_comparative_reflections_b7391003_study_for_pf_06439535_a_potential_biosimilar_to_avastin_1_bevacizumab. Accessed June 2019.
Philadelphia, PA (February 22, 2019) – Oncoceutics, Inc., announces the expansion of its diverse collaborations across the National Institutes of Health (NIH) involving its imipridone family of anti-cancer compounds.
ONC206 has been studied extensively for several years in models of central nervous system cancers, including high grade gliomas as evaluated by the laboratory of Mark Gilbert, MD, Chief of the Neuro-Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI). These studies convincingly demonstrate that ONC206 exerts significant therapeutic effects on preclinical models of brain cancers that are commonly recognized as incurable. The properties of ONC206 that include penetrance of the blood brain barrier, feasibility of oral administration, demonstration of a benign safety profile in preclinical studies, and selective antagonization of dopamine receptor D2 (DRD2) further demonstrate the potential therapeutic value of the new class of imipridone compounds. While DRD2 is targeted by ONC206, as well as the first clinical-stage imipridone ONC201, the receptor pharmacology of ONC206 is unique, offering therapeutic options beyond ONC201.
Based upon NCI’s positive data from preclinical studies of ONC206, Dr. Mark Gilbert and his team in the Neuro-Oncology Branch, CCR, NCI in Bethesda, MD, are interested in conducting the first-in-human trial of ONC206 following Oncoceutics’ completion of IND-enabling studies and the execution of an appropriate agreement. This clinical trial will incorporate biomarker information derived from the molecular mechanism of ONC206 to select patients and to profile its activity in patients with central nervous system malignancies.
“I am excited to see ONC206, as the second imipridone, on the verge of entering the clinic,” Minesh Mehta, MD, Deputy Director And Chief Of Radiation Oncology, Miami Cancer Institute and member of the board of directors of Oncoceutics. “This translational effort will introduce ONC206 as an impactful new therapy for patients with untreatable brain tumors and broadens the clinical utility of imipridones beyond its founding member, ONC201, which is already helping patients."
Oncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds, called “imipridones,” that selectively target G protein-coupled receptors for oncology. The first lead compound to emerge from this program is ONC201, an orally active small molecule DRD2 antagonist. The company is supported by grants from NCI, FDA, Musella Foundation, XCures, Cancer Commons, and a series of private and public partnerships.
Visit Oncoceutics for more information.
On March 8, the FDA granted the accelerated approval of Roche’s programmed cell death protein 1 (PD-1) inhibitor Tecentriq in combination with Abraxane (protein-bound paclitaxel) for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC).
Adam Pearson, PhD, Oncology and Hematology Analyst at GlobalData, a leading data and analytics company, offers his view on the FDA approval of Tecentriq for TNBC:
“The emergence of Tecentriq as the first-in-class PD-1 inhibitor in breast cancer marks the first approval of an immuno-oncology drug in breast cancer and signifies the introduction of a new treatment strategy in a therapeutically elusive subset of breast cancer. It represents a win for Roche in a PD-1 inhibitor market dominated by Merck & Co.’s Keytruda and Bristol-Myers Squibb’s (BMS) Opdivo. Tecentriq is poised to temporarily monopolize the TNBC market until Merck & Co. is expected to release its Keytruda data from two Phase III trials this year.
“Therefore, despite the first-in-class success for Tecentriq in TNBC, Merck & Co.’s active testing of Keytruda in a single-agent setting and in combination with chemotherapy of physician’s choice, may ultimately allow Keytruda to be used in broader patient populations.
“Further opportunities exist in the neoadjuvant/adjuvant setting, in hormone-receptor-positive, and HER-2-positive breast cancers and finally, through novel combinations of PD-1 inhibitors with the approved poly ADP ribose polymerase (PARP) inhibitors in breast cancer patients harboring BRCA1 (breast cancer type 1 susceptibility protein) mutations. Each is an active area of investigation.
“Needless to say, competition will be fierce and each of the immuno-oncology players will strive to carve out a therapeutic niche within the breast cancer market.”
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SOUTH SAN FRANCISCO, Calif., April 2, 2019 /PRNewswire/ -- ORIC Pharmaceuticals, a privately held, clinical-stage oncology company focused on the discovery and development of novel therapies against treatment-resistant cancers, today presented new preclinical data on its lead program ORIC-101, a selective and potent glucocorticoid receptor (GR) antagonist, at the American Association of Cancer Research (AACR) Annual Meeting in Atlanta, GA.
The data were presented in a poster "ORIC-101 Reverses a GR-Driven EMT-like Phenotype and Sensitizes TNBC Cells to Chemotherapy (Abstract #3822)" during the Experimental and Molecular Therapeutics poster session.
The Company's research findings provide insight into the molecular basis of GR-mediated resistance to chemotherapy in triple-negative breast cancer (TNBC). GR was found to activate multiple biological pathways involved in therapy resistance, including epithelial-mesenchymal transition (EMT), stemness and anti-apoptosis. Using a murine TNBC xenograft model, oral administration of ORIC-101 reversed these effects and restored sensitivity to chemotherapy.
The Company plans to initiate multiple Phase 1b studies of ORIC-101 in combination with other anti-cancer agents in patients with advanced solid tumors, the first of which is expected to initiate in the second quarter of 2019.
About ORIC Pharmaceuticals
ORIC Pharmaceuticals is a privately held, clinical-stage oncology company focused on making cancer treatments more effective by addressing mechanisms of resistance. ORIC's lead asset, ORIC-101, is a potent and selective small molecule antagonist of the glucocorticoid receptor. ORIC's pipeline also includes an orally-available small molecule inhibitor of CD73, as well as other undisclosed programs targeting mechanisms of oncology therapy resistance. ORIC's scientific founders are Charles Sawyers, MD, and Scott Lowe, PhD, who have strong records of discovering novel targets in cancer that have led to innovative treatments. The company has assembled strong leadership and scientific teams and a board with extensive experience in drug development and financing. ORIC is funded by leading biotechnology investors, including The Column Group, Topspin Partners, OrbiMed, EcoR1, Fidelity, Foresite and others. ORIC is headquartered in South San Francisco, California.
SOURCE Oric Pharmaceuticals
NEW DATA SHOW BLUEPRINT® IDENTIFIES ESTROGEN RECEPTOR POSITIVE BREAST CANCER PATIENTS WITH POOR RESPONSE TO ANTI-ESTROGEN THERAPY WHO MAY BENEFIT FROM NEOADJUVANT CHEMOTHERAPY
ER+ breast cancer patients reclassified as ER+ basal-type demonstrated significant response to chemotherapy underscoring critical role of advanced diagnostic tools
Results published in Nature Publishing Group’s npj Breast Cancer
IRVINE, CALIF., U.S., and AMSTERDAM, NETHERLANDS –24 April, 2019 – Agendia, Inc., a world leader in precision oncology, today announced the publication of study results for BluePrint®, its 80-gene proprietary molecular subtyping test, in Nature Breast Cancer. It is well known that a significant subset of patients diagnosed with early stage, estrogen receptor (ER) positive (ER+) breast cancer appear to be poorly responsive to standard anti-estrogen therapy and may benefit significantly to the addition of chemotherapy. This latest study suggests that use of BluePrint® can more precisely predict tumor response to treatment and clinical outcome.
Published this week, the study, “Estrogen Receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers” sought to conduct a molecular analysis and clinical follow up of patients that were reclassified as ER+ Basal-type (n=91) in the Neoadjuvant Breast Registry Symphony Trial (NBRST) (n=1072). The results of the analysis showed:
Pat Whitworth, MD, Director, Nashville Breast Center and study author said, “Traditionally, the medical community has been challenged by a certain subtype of ER+ tumors that respond poorly to standard treatment. These “bad actors” read out as ER+ on standard assays even though their ER does not function well in the cell. This study shows that through diagnostic tools like BluePrint®, we now have the ability to predict and identify how a tumor might respond to treatment that goes beyond traditional molecular classifiers, to seeing the fundamental biology of an individual tumor. This diagnostic step is critical to ensuring patients get the right treatment from the start, and helps drive better long-term outcomes.”
In partnership with the Breast Cancer Research Foundation (BCRF), NBRST took breast cancers categorized by traditional pathology measures (immunohistochemistry or IHC) as ER-positive (ER+), and molecularly reclassified them with BluePrint® into one of three subtypes – Luminal, HER2 or Basal – based on gene expression patterns. Thirteen percent of these ER+ patients were reclassified as having Basal-type breast cancer and were observed to have similar clinical outcomes and response to therapy as “triple-negative” breast cancer which typically indicates chemotherapy as standard treatment. Similar to patients with triple-negative breast cancer, these ER+ Basal-type patients experienced a six-fold increase in pathologic complete response (pCR) to neoadjuvant chemotherapy compared to other ER+ patients, which resulted in significant improvement in long-term outcomes.
“What we now understand is that a diagnosis of breast cancer may encompass up to a dozen distinct diseases, all with differing prognoses and treatments. This data offers additional clarity to the oncology community’s understanding of the complexity of breast cancer, and provides further data regarding this clinically important subset of ER+ cancers. Because routine pathology cannot reliably distinguish these cancers, identifying these ER+ Basal-type cancers through subtyping with BluePrint® provides valuable new information for the optimal management of early breast cancer,” added William Audeh, MD, Medical Oncologist and Agendia Chief Medical Officer.
The study is available open access and can be found on-line at https://rdcu.be/bxGN9.
MammaPrint is an in vitro diagnostic medical device, performed as a testing service in a central laboratory, using the 70-gene expression profile of breast cancer tissue samples to assess a patient’s risk for distant metastasis. The device is FDA-cleared and CE-marked, enabling use in the European Union. MammaPrint is indicated for use by physicians as a prognostic marker only, along with other clinical-pathological factors. It is not intended to determine the outcome of disease, nor to suggest or infer an individual patient’s response to therapy. MammaPrint is the only test of its kind recommended for lymph node-negative and lymph node-positive patients by both the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN®). The test is also recommended by many other national and international clinical practice guidelines.
BluePrint® is an 80-gene complementary gene expression test provided with MammaPrint which allows functional molecular subtyping of a breast cancer sample into three distinct subtypes: Luminal-type, HER2-type and Basal-type, each with marked differences in long-term outcome and response to neoadjuvant chemotherapy.
Agendia is a privately held, leading precision oncology company focused in breast cancer that develops and markets genomic diagnostic products, which help support physicians with their complex treatment decisions. Agendia’s breast cancer tests were developed using an unbiased gene selection by analyzing the complete human genome. The company’s offerings include the MammaPrint Breast Cancer Risk-of-Recurrence Test, and the BluePrint® Molecular Subtyping Test, both on microarray technology, whereas the new MammaPrint BluePrint® Breast Cancer Recurrence and Molecular Subtyping Kit, is on NGS technology. The MammaPrint BluePrint® next-generation sequencing-based kit is a CE-marked device currently available for use in cancer centers in select regions of the world. In addition, Agendia has a pipeline of other genomic products in development. The company collaborates with pharmaceutical companies, leading cancer centers and academic groups to develop companion diagnostic tests in the area of oncology. For more information on Agendia or the MammaPrint and BluePrint® tests, visit www.agendia.com.