On November 15, 2017 ONCODESIGN (Paris:ALONC) (ALONC – FR0011766229), a biopharmaceutical group specialized in , precision medicine, reported that it has obtained positive results opening the way for the ALK1 kinase inhibitor discovery program to move on to the lead optimization phase (Press release, Oncodesign, NOV 15, 2017, View Source [SID1234522101]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ALK1 is a kinase involved in angiogenesis. Tumoral angiogenesis is the mechanism by which new blood vessels form and infiltrate tumors to provide nutrients and oxygen and to dispose of the tumor’s cellular waste products. Inhibiting this mechanism is a promising line of research in the quest for new treatments for most types of cancer.

The ALK1 program has produced positive cellular results in a mechanistic model as part of the probe to lead phase. Oncodesign has thus decided to advance it to the lead optimization phase and commence an exhaustive series of in vivo biological tests, while conducting medicinal chemistry optimization of the inhibitor molecules identified. A medicinal chemistry team dedicated to the project will be set up to implement this decision.

"At the end of the Lead Optimization phase a drug candidate could be selected for preclinical trials and then clinical development", said Jan Hoflack, Oncodesign’s Chief Scientific and Operating Officer. "Today, our preclinical portfolio contains no fewer than 12 programs, and ALK1 is joining our most advanced programs. Our goal is to develop a best-in-class drug from this program with the potential to complement other anti-angiogenic approaches, currently a market worth over $10 billion. The addition of the drug discovery expertise of the François Hyafil research center in Paris-Saclay has enabled us to accelerate our most promising programs significantly. ALK1 is the first example of a project successfully moving on to a major new stage in its development by harnessing this new expertise."

After exploring molecules’ therapeutic potential in the probe qualification and probe orientation stages, molecules move on to the probe to lead phase. Molecules then undergo a further selection stage after medicinal chemistry optimization of their structure, and the programs are prioritized according to their activity in relevant cell models and their potential to become a drug.

The lead optimization phase aims to identify a drug candidate, a molecule meeting a large number of very exacting criteria to determine its suitability as a future drug. The selection of a drug candidate takes place at the end of the drug discovery phase, and the regulatory development phases then begin. Lead optimization can take up to 36 months, and the success rate is typically around 50%.

About kinases and Nanocyclix technology:

Kinases are a family of enzymes that play a key role in regulating most cell functions, such as proliferation, cell cycle progression, metabolism, survival/apoptosis, repair of damaged DNA, motility and response to the microenvironment.
Using its Nanocyclix technology module, Oncodesign identifies macrocyclic molecules capable of inhibiting both known and unexplored kinases in a powerful and targeted manner. A large variety of kinase inhibitors are thus explored continuously, and only the most promising inhibitor/targeted kinase combinations are selected for more in-depth investigations.
Oncodesign has built a project portfolio with tremendous potential to treat diseases with very substantial unmet medical needs. This portfolio contains both molecules already at an advanced stage of clinical development (a PET tracer for a specific type of lung cancer) and molecules at an earlier stage of development.

On November 15, 2017 Moderna Therapeutics, a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported that it has started dosing patients in a Phase 1 study of mRNA-4157, an mRNA-based personalized cancer vaccine (Press release, Moderna Therapeutics, NOV 15, 2017, View Source [SID1234522100]). The Phase 1 open-label, dose escalation, multicenter study in the United States (KEYNOTE-603) will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, marketed by Merck (known as MSD outside the U.S. and Canada) in subjects with unresectable solid tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The first-in-human dosing of mRNA-4157 marks a key milestone in the strategic collaboration between Moderna and Merck to advance the novel mRNA-based personalized cancer vaccine in combination with KEYTRUDA for the treatment of multiple types of cancer.

"When we combine the potential for robust T-cell response stimulated by our mRNA vaccine, which encodes for 20 patient-specific mutations, with Merck’s checkpoint inhibitor, Keytruda, we have a unique opportunity to make a transformative difference for patients with cancer," said Tal Zaks, M.D., Ph.D., Chief Medical Officer at Moderna. "Having now successfully designed, manufactured and dosed a completely customized personalized cancer vaccine, we look forward to progressing the Phase 1 clinical study and gathering important human data on mRNA-4157 in the months ahead."

KEYNOTE-603 is expected to enroll up to 90 patients across multiple clinical study sites in the United States. Part A of the study will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors (in the adjuvant setting). Part B of the study will evaluate mRNA-4157 in combination with KEYTRUDA in subjects with unresectable solid tumors. The ClinicalTrials.gov Identifier for the mRNA-4157 study is: NCT03313778. A link to the ClinicalTrials.gov listing for the study can be found here.

"Our goal in this important collaboration is to deliver personalized vaccines to patients suffering from malignant disease, with the hope that this stimulus will generate a tumor-specific immune response in the presence of Keytruda, our approved immune-stimulatory cancer therapy," said Roger M. Perlmutter, M.D., Ph.D., President, Merck Research Laboratories. "This trial leverages advances in genomics, advanced data analytics, and immunology to permit the generation of personalized cancer vaccines, a potentially transformative approach to cancer treatment. We are hopeful that this collaboration with Moderna, now entering clinical trials, will yield tangible benefits for cancer patients."

"Checkpoint inhibitors and other immuno-oncology therapies are continuing to revolutionize how we treat cancer. However, despite the strong and durable responses we see in some patients, many other patients’ disease continues to progress," said Howard A. "Skip" Burris III, MD, President, Clinical Operations & Chief Medical Officer at Sarah Cannon, and a Principal Investigator of the mRNA-4157 Phase 1 study. "An individualized medicine designed to help each patient’s immune system better recognize cancer as foreign and attack it would be a critical addition to oncologists’ treatment arsenal, potentially helping many more patients respond more effectively to treatment."

About mRNA-4157

Moderna is creating an individualized, mRNA-based personalized cancer vaccine to deliver one medicine for one patient at a time. Through next-generation sequencing, Moderna identifies mutations found on a patient’s cancer cells, called neoepitopes. Neoepitopes can help the immune system distinguish cancer cells from normal cells. Using algorithms developed by its in-house bioinformatics team, Moderna predicts 20 neoepitopes present on the patient’s cancer that should elicit the strongest immune response, based on unique characteristics of the patient’s immune system and particular mutations. Moderna then creates a vaccine that encodes for each of these mutations and loads them onto a single mRNA molecule.

Once injected into the patient, the vaccine should direct the patient’s cells to express the selected neoepitopes. In turn, this may help the patient’s immune system better recognize cancer cells as foreign and destroy them. Leveraging its rapid cycle time, small-batch manufacturing technique and digital infrastructure, Moderna plans to manufacture and supply each individually manufactured personalized cancer vaccine to patients within weeks.

mRNA-4157 also has the potential to enhance clinical outcomes associated with checkpoint inhibitor therapies. In 2016, Moderna and Merck formed a collaboration to develop mRNA-4157 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA.

About the Moderna and Merck Collaboration to Advance mRNA-4157

Under the terms of the agreement announced in June 2016, Merck made an upfront cash payment to Moderna of $200 million, which Moderna is using to lead all research and development efforts through proof of concept. The development program will entail multiple studies in several types of cancer and include the evaluation of mRNA-4157 in combination with KEYTRUDA. Moderna is also utilizing the upfront payment to fund a portion of the ongoing build-out of its GMP mRNA clinical manufacturing facility in Norwood, Mass., for the purposes of personalized cancer vaccine manufacturing.

Following human proof of concept studies, Merck has the right to elect to make an additional undisclosed payment to Moderna. If exercised, the two companies will then equally share cost and profits under a worldwide collaboration for the development of mRNA-4157. Moderna will have the right to elect to co-promote mRNA-4157 in the U.S. The agreement entails exclusivity around combinations with KEYTRUDA. Moderna and Merck will each have the ability to combine mRNA-4157 with other immuno-oncology (non-PD-1) agents.

On November 15, 2017 EUSA Pharma and AVEO Oncology (NASDAQ:AVEO) reported the first commercial launch of FOTIVDA (tivozanib) with the initiation of product sales in Germany (Press release, AVEO, NOV 15, 2017, View Source;p=RssLanding&cat=news&id=2317048 [SID1234522076]). In the European Union, Norway and Iceland, tivozanib is indicated for the first line treatment of adult patients with advanced renal cell carcinoma (aRCC) and for adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for aRCC.i Tivozanib is an oral, once-daily, potent and highly-selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI). EUSA Pharma is the licensee for tivozanib in Europe, North and South Africa, Latin America and Australasia.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lee Morley, EUSA Pharma’s Chief Executive Officer said, "We are delighted that we have been able to grant access to FOTIVDA for patients in one of Europe’s key markets so soon after our regulatory approval. We look forward to working with physicians in Germany to ensure the profile and benefits of FOTIVDA are known and understood. We will of course continue to work with health authorities across all European markets to ensure early access to FOTIVDA as a therapeutic option in the ongoing fight against aRCC."

"The first-ever commercial launch of FOTIVDA is a tremendous accomplishment for AVEO, our partner EUSA Pharma, and, most importantly, patients with aRCC who now have access to a new and differentiated therapeutic option," said Michael Bailey, president and chief executive officer of AVEO. "Over the course of its development, FOTIVDA’s efficacy and tolerability profile among VEGF TKIs has been recognized by investigators as an important potential option for their patients, making this long-anticipated milestone a gratifying achievement. We continue to leverage this profile as we work towards exploring the full extent of FOTIVDA’s use in the emerging aRCC market. We also look forward to continuing to expand its availability in Europe, through our partner, EUSA, and potentially in North America, where we plan to file for FDA approval pending the results of our pivotal study, TIVO-3."

FOTIVDA was approved by the European Commission in August 2017. Approval was primarily based on data from a global, open-label, randomized, multi-center Phase 3 trial (TIVO-1)i,ii which evaluated the efficacy and tolerability of tivozanib compared to a currently available comparator VEGFR-TKI treatment (sorafenib) in 517 patients with advanced RCC. Patients treated with tivozanib experienced superior PFS (11.9 vs. 9.1 months in the overall population [HR, 0.797; 95% CI, 0.639 to 0.993; P =.042] and 12.7 vs. 9.1 months in treatment naïve patients [HR, 0.756; 95% CI, 0.580 to 0.985; P =.037]) versus sorafenib.ii There was also an improved side effect profile with tivozanib, with only 14% (versus 43% with sorafenib) requiring a dose reduction due to adverse events (AEs). In addition, fewer people on tivozanib experienced burdensome side effects, such as diarrhea (23% vs 33%) and hand-foot syndrome (14% vs 54%).ii

About RCC in Europe

RCC is the most common form of kidney cancer,iii which accounts for an estimated 49,000 deaths in Europe each year.iv It is expected to be one of the fastest increasing cancers over the next ten years.v Tyrosine Kinase Inhibitor (TKI) vascular endothelial growth factor (VEGF) inhibitors are the standard of care treatment for advanced RCC in Europe, however, patients on current treatments can often experience significant side effects.ii,vi

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.i,ii Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

On November 15, 2017 AstraZeneca reported that the US Food and Drug Administration (FDA) has approved a new indication for Faslodex (fulvestrant), expanding the indication to include use with abemaciclib, a CDK4/6 inhibitor, for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer (MBC) in women with disease progression after endocrine therapy (Press release, AstraZeneca, NOV 15, 2017, View Source [SID1234522075]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: "Faslodex has long been an effective monotherapy option for women with hormone receptor positive breast cancer, which is the most common type of advanced breast cancer. Today’s decision builds upon the recent approval for Faslodex in the first-line advanced setting and is supported by strong evidence to use this medicine within a combination therapy for advanced breast cancer. Combining Faslodex with abemaciclib provides patients with another effective, non-chemotherapy option to combat this disease."

Peter A. Kaufman, MD of the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, said: "This new indication for Faslodex offers another treatment option for women living with HR+, HER2- advanced or metastatic breast cancer with disease progression after endocrine therapy. The study supporting this indication demonstrated that Faslodex used in combination with abemaciclib significantly improves progression-free survival compared to Faslodex and placebo."

The FDA approval is based on data from the Phase III MONARCH 2 trial, which met the study’s primary endpoint of PFS.

The trial included 669 women with HR+, HER2- advanced breast cancer. The results showed a statistically significant increase in investigator-assessed median PFS of 7.1 months (16.4 months vs 9.3 months) in patients who received Faslodex 500 mg and abemaciclib 150 mg over Faslodex and placebo (HR: 0.553; 95% CI: 0.449-0.681; p<0.0001).

This expanded indication for Faslodex is the second FDA approval for Faslodex in combination with a CDK4/6 inhibitor. Faslodex has been licensed in the US since 2016 for use with the CDK4/6 inhibitor, palbociclib, for the treatment of women with HR+, HER2-negative MBC, whose cancer has progressed after endocrine therapy.

NOTES TO EDITORS
About MONARCH 2

MONARCH 2 is a Phase III, international, randomised, double-blind, placebo-controlled, multicenter study, sponsored by Eli Lilly and Company, of Faslodex with abemaciclib vs Faslodex with placebo conducted in women with HR+, HER2- advanced or metastatic breast cancer, whose disease progressed on or after neoadjuvant or adjuvant endocrine therapy, ≤12 months from the end of adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease. The study included 669 women randomly assigned to receive intramuscular injection of 500 mg Faslodex with abemaciclib or placebo orally twice daily in a 2:1 ratio. Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin acetate for at least four weeks prior to and for the duration of the study. Patients remained on treatment until development of progressive disease or unmanageable toxicity.

Patients enrolled in this study had a median age of 60 years (range, 32 to 91). The majority of patients in the study were white (56%). All patients had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.

Approximately 59% of patients in each of the treatment arms, Faslodex in combination with abemaciclib and Faslodex with placebo, received endocrine therapy as their first therapy for advanced breast cancer; the remaining 38% of patients in the experimental and in the control treatment arms received this regimen as their second endocrine therapy for advanced breast cancer. 55.8% had visceral disease and 26.9% had bone-only disease. Twenty-five percent of patients had primary endocrine resistance, and 2.7% had locally advanced disease.

Detailed results of the MONARCH 2 trial are published online in the Journal of Clinical Oncology.

About Advanced Breast Cancer or Metastatic Breast Cancer (MBC)

Advanced/metastatic breast cancer refers to Stages III and IV breast cancer. Stage III disease may be referred to as locally-advanced breast cancer. MBC is the most advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumor site to other parts of the body outside of the breast.

Despite treatment options increasing during the past three decades, there is currently no cure for patients diagnosed with MBC and the 5-year relative survival rate for this patient population is currently 26.9%. Thus, the primary aim of treatment is to slow progression of the disease for as long as possible, improving, or at least maintaining, a patient’s quality of life.

It is estimated that in 2017, there will be approximately 153,000 women in the US living with MBC, and this number is projected to increase to approximately 160,000 by the year 2020.

About Faslodex (fulvestrant)

Faslodex is indicated for the treatment of oestrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on anti-oestrogen therapy.

In the US, EU and Japan, Faslodex is also approved in combination with palbociclib for the treatment of women with HR+, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the oestrogen receptor – a key driver of disease progression.

Faslodex is approved in over 80 countries as a monotherapy to treat ER+ advanced breast cancer patients. It is currently being evaluated in combination with medicines from various drug classes for the treatment of women with HR+ advanced breast cancer.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On November 15, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast a management presentation at the 29th Annual Piper Jaffray Healthcare Conference at 4:00 p.m. ET on Tuesday, November 28, 2017 (Press release, Regeneron, NOV 15, 2017, View Source [SID1234522097]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The session may be accessed through the Company’s web site, www.regeneron.com, on the ‘Events and Presentations’ page. An archived version of the presentation will be available for 30 days.