On March 2, 2017 Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response therapeutics for the treatment of patients with cancer, reported its financial and operational results for the year ended December 31st, 2016 (Press release, Sierra Oncology, MAR 2, 2017, View Source [SID1234517984]). Schedule your 30 min Free 1stOncology Demo! "We relaunched as Sierra Oncology in January 2017, with a stated focus on developing oncology drugs targeting the DNA Damage Response (DDR) network. Recently, we successfully transferred sponsorship of the two ongoing Phase 1 clinical trials for our lead DDR drug candidate SRA737 to the company, which enabled us to submit protocol amendments aimed at enhancing both of these studies," said Dr. Nick Glover, President and CEO of Sierra Oncology. "In particular, as synthetic lethality due to Chk1 inhibition has been linked to certain classes of genetic alterations, we plan to focus enrollment in these trials on prospectively-selected patients predicted to most likely derive benefit from SRA737 treatment based on the genetics of their tumors. A preliminary update from the SRA737 clinical trials is anticipated to be available around the end of 2017."
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"We believe SRA737 has the opportunity to expand beyond the scope of PARP inhibitors, and we have ambitious plans for developing this potential best-in-class Chk1 inhibitor. In February 2017, we raised additional capital to facilitate advancing SRA737 into the next wave of its development. Beyond enhancing the current monotherapy and chemotherapy combination trials, this will involve preparing for potential combination studies of SRA737 with PARP inhibitors and immuno-oncology agents," added Dr. Glover.
Potential SRA737 Monotherapy Trial Enhancements
SRA737 is currently being evaluated in two clinical trials in patients with advanced cancer. The first trial is intended to evaluate SRA737’s potential to induce synthetic lethality as monotherapy. Sierra intends to amend the monotherapy clinical trial protocol in order to evaluate the preliminary efficacy of SRA737 in subjects with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition. Additionally, Sierra intends to modify the study to assess SRA737’s clinical activity across a number of cancer indications that harbor these genetic mutations in order to determine potential patient selection strategies for further clinical development.
Following the anticipated approval and activation of the planned protocol amendment, an algorithm based on genetic selection will be employed in order to guide patient selection. The algorithm is intended to define patient enrollment where the subject’s tumor has a confirmed minimum of two different types of genetic abnormalities. These could include tumors with a deleterious mutation in a key tumor suppressor gene, such as TP53, and at least one of the following:
a loss of function or deleterious mutation in the DNA damage response pathway such as ATM, BRCA1, BRCA2, or another gene in the DNA damage response pathway implicated in Chk1 pathway sensitivity;
a genetic indicator of replicative stress, defined as gain of function or amplification of CHEK1 or ATR or other related gene; or
a gain of function mutation or amplification of an oncogenic driver such as MYC, RAS, or another gene implicated in Chk1 pathway sensitivity.
Cancers that are predicted to have a high prevalence of genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition are planned to be evaluated in the amended clinical trial within tissue-specific expansion cohorts. These include, for example, cohorts of subjects with:
previously treated metastatic colorectal cancer;
platinum-resistant ovarian cancer;
metastatic castration-resistant prostate cancer;
advanced non-small cell lung cancer; and
head and neck squamous cell carcinoma.
Potential SRA737 Chemotherapy Combination Trial Enhancements
Sierra intends to enhance the chemotherapy combination clinical trial underway by modifying the clinical trial design in order to evaluate the preliminary efficacy of SRA737 in expansion cohorts comprising subjects with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition. The company intends to employ a similar genetic selection algorithm to that defined in the monotherapy protocol. Specifically, the company plans to enroll subjects with bladder cancer and pancreatic cancer into genetically-selected dose expansion cohorts, as (i) bladder cancer and pancreatic cancer are predicted to have a high prevalence of genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition and (ii) gemcitabine is often an important component of the standard of care treatment for these indications.
Year-End 2016 Financial Results (all amounts reported in U.S. currency)
Research and development expenses increased to $33.9 million for the year ended December 31, 2016 from $26.4 million for the year ended December 31, 2015. These increases in 2016 were primarily due to a $7.0 million upfront fee due to CRT Pioneer Fund LP (CPF) for the exclusive license of SRA737, the recognition of a $2.0 million fee due upon the successful transfer of two ongoing clinical trials in accordance with the SRA737 license agreement and a $0.9 million upfront fee paid to Carna Biosciences, Inc. for the exclusive license of SRA141. The remaining increase was attributable to a $4.5 million increase in personnel-related costs, a non-recurring $2.2 million restructuring charge related to estimated close-out expenses for PNT2258, and an $0.7 million increase in other research costs and allocated overhead expenses. These were partially offset by a $6.7 million decrease in third-party manufacturing costs and a $3.1 million decrease in clinical trial costs primarily due to the halting of further investment in PNT2258.
General and administrative expenses increased to $14.2 million for the year ended December 31, 2016 from $9.5 million for the year ended December 31, 2015. This increase was primarily due to a $2.3 million increase in personnel-related costs and fees incurred in support of corporate growth, a $1.1 million increase related to business development activities, a $0.8 million increase in allocated overhead expenses and a $0.5 million non-recurring restructuring charge.
Total operating expenses for the year ended December 31, 2016 were $48.1 million compared to $35.8 million for the year ended December 31, 2015. Total operating expenses included non-cash stock based compensation of $5.5 million for the year ended December 31, 2016 and of $3.2 for the year ended December 31, 2015, respectively.
For the year ended December 31, 2016, Sierra Oncology incurred a net loss of $47.9 million compared to a net loss of $53.3 million for the year ended December 31, 2015. During the year ended December 31, 2015, net loss included a non-cash charge related to the change in fair value of preferred stock warrants of $17.4 million.
At December 31, 2016, Sierra Oncology had $109.0 million in cash and cash equivalents compared to $150.2 million in cash and cash equivalents at December 31, 2015. At December 31, 2016, there were 30,370,946 shares of common stock issued and outstanding and stock options to purchase 6,543,654 shares of common stock issued and outstanding.
Subsequent to the end of the year, Sierra Oncology paid the $2.0 million fee due to CPF for the successful transfer of the two ongoing clinical trials for SRA737. In February 2017, Sierra Oncology completed an underwritten public offering of 21,847,636 shares of common stock, raising aggregate net proceeds of $27.3 million from the offering, net of underwriting discounts and commissions and estimated offering expenses. We believe that our existing cash and cash equivalents will be sufficient to fund our current operating plans through approximately mid-2019.
Month: March 2017
Synthon enters worldwide exclusive license and collaboration with Sanquin for immuno-oncology therapeutic leads modulating the CD47-SIRPα pathway
On March 2, 2017 Synthon Biopharmaceuticals BV, an international biopharmaceutical company that is focused on developing new molecular entities for treating cancer and autoimmune diseases, reported that it has entered a license and collaboration agreement for the development of novel immuno-oncology antibodies with Sanquin Blood Supply Foundation (‘Sanquin’), Amsterdam (Press release, Synthon, MAR 2, 2017, View Source [SID1234517973]). Schedule your 30 min Free 1stOncology Demo! Under the terms of the agreement, Synthon has obtained worldwide exclusive rights to Sanquin’s know-how, lead antibodies and intellectual property regarding the CD47-SIRPα pathway to develop new immuno-oncology treatments.
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CD47 is a broadly expressed membrane protein that interacts with the myeloid inhibitory immunoreceptor SIRPα (also termed CD172a or SHPS-1). When SIRPα engages with CD47, it provides a downregulatory signal that inhibits host cell phagocytosis, and CD47 therefore acts as a "don’t-eat-me" signal. Blocking CD47-SIRPα interactions promotes the destruction of, for example, cancer cells by phagocytes through antibody-dependent mechanisms.
Dr. Marco Timmers, chief scientific officer of Synthon Biopharmaceuticals commented: "We are particularly pleased with this license and collaboration agreement, which combines Sanquin’s outstanding research capabilities with Synthon’s biopharmaceutical drug development and manufacturing excellence. This will enable us to accelerate the availability of important new therapeutic treatment options for cancer patients who may benefit from these."
Prof. Dr. René van Lier, director of Research and Member of the Executive Board at Sanquin: "The collaboration agreement with Synthon, with their knowledge of next-generation medicines, is a great example of Sanquin’s efforts to provide patients with innovative therapeutic treatment options."
Financial details of the agreement were not disclosed.
Boehringer Ingelheim expands collaboration with Vanderbilt University to tackle some of the most difficult-to-treat cancers
On March 2, 2017 Boehringer Ingelheim reported a new collaboration with Vanderbilt University, Nashville, Tennessee (Press release, Boehringer Ingelheim, MAR 2, 2017, https://www.boehringer-ingelheim.com/press-release/next-generation-cancer-treatment-collaboration [SID1234517972]). The multi-year program complements an already existing collaboration by focusing on the research and development of small molecule compounds targeting the protein SOS (Son Of Sevenless). This molecule activates KRAS, a molecular switch that plays a central role in the onset of some of the deadliest cancers.
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The collaboration combines pioneering research in the laboratory of Stephen W. Fesik, Orrin H. Ingram II professor in cancer research at Vanderbilt University, with the unique expertise and strength of Boehringer Ingelheim in drug discovery and clinical development. The new collaboration adds to an ongoing joint project with Vanderbilt University initiated in 2015 that achieved two major milestones by identifying lead compounds that bind to KRAS with high affinities. These discoveries raise the prospect of developing novel cancer treatment options based on molecules that are able to block this critical cancer driver.
"We are very encouraged by the successful identification of inhibitors of KRAS in our alliance with Professor Fesik and his team at Vanderbilt University and look forward to expanding our collaboration," said Clive R. Wood, Ph.D., senior corporate vice president, discovery research at Boehringer Ingelheim. "With new technologies and the scientific discoveries made by Professor Fesik’s laboratory, we believe the time is now right to step up research efforts to develop novel cancer treatments that work by attacking KRAS and associated signaling pathways."
"Professor Fesik is a pioneer in the discovery of small molecules that bind to and inhibit challenging drug target proteins. His partnership with Boehringer Ingelheim will expedite efforts to discover novel cancer treatments that work on KRAS," said Lawrence J. Marnett, Ph.D., the Mary Geddes Stahlman professor of cancer research, university professor of biochemistry and chemistry and dean of basic sciences for the Vanderbilt University School of Medicine.
Mutations in the genes that encode KRAS are among the most powerful and frequent cancer drivers. They contribute to some of the most aggressive and deadly cancers, including up to 25 percent of lung, 35-45 percent of colorectal and about 90 percent of pancreatic tumors. KRAS has been a particularly difficult protein to target and no effective treatments targeting KRAS have been developed since its discovery in human cancers more than 30 years ago. The development of the first molecules inhibiting KRAS activation promises huge potential for the development of improved cancer therapies, which would offer treating physicians unprecedented options to complement existing treatment regimens.
By researching multiple approaches including direct inhibition of KRAS and indirect inhibition via SOS, Boehringer Ingelheim aims to accelerate the discovery of novel targeted therapies. The new collaboration with Vanderbilt University further strengthens Boehringer Ingelheim’s oncology pipeline, which focuses on tumor cell-directed cancer treatments, new approaches in immune oncology and their combinations. It underscores the companies’ commitment to pioneering emerging fields of research and working closely with its partners to accelerate the development of novel first-in-class, breakthrough medications that fit the needs of patients, caregivers and healthcare professionals.
Mersana Presents New Data on Investigational Cancer Antibody Drug Conjugate at American Association of Cancer Research Annual Meeting
On March 2, 2017 Mersana Therapeutics, Inc., a biotechnology company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) based on its Fleximer platform technology, reported that it will present data on its lead preclinical immunoconjugate, XMT-1522, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington, D.C (Press release, Mersana Therapeutics, MAR 2, 2017, View Source [SID1234517971]). The two poster presentations will highlight results from ongoing non-clinical studies where the compound was evaluated as a potential combination partner with immunomodulatory cancer therapies and it was also characterized for its pharmacokinetics, metabolism and biodistribution in tumor-bearing mice. Schedule your 30 min Free 1stOncology Demo!
The accepted abstracts are listed below and are now available online on the AACR (Free AACR Whitepaper) 2017 conference website: www.aacr.org
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Abstract Control Number: 6879
Title: Combination of anti-HER2 ADC XMT-1522 and checkpoint inhibitor pembrolizumab for treatment of NSCLC in preclinical models
Authors: Natasha Bodyak, Marina Protopopova, Qingxiu Zhang, Alex Yurkovetskiy, Mao Yin, LiuLiang Qin, Laura L Poling, Rebecca Mosher, Donald A. Bergstrom, Timothy B. Lowinger
Session Category: Immunology
Session Title: Immune Response to Hematopoietic Tumors: New Developments in Tumor Immunology
Session Date and Time: Monday Apr 3, 2017 1:00 PM – 5:00 PM
Location: Convention Center, Halls A-C, Poster Section 26
Poster Board Number: 29
Abstract control number: 6716
Title: Non-clinical pharmacokinetics of XMT-1522, a HER2 targeting auristatin-based antibody drug conjugate.
Authors: Donald A. Bergstrom, Natalya Bodyak, Alex Yurkovetskiy, Michael DeVit, Mao Yin, Laura L. Poling, Joshua D. Thomas, Dmitry Gumerov, Dongmei Xiao, Elena Ter-Ovanesyan, Charlie Bu, LiuLiang Qin, Alex Uttard, Alex Johnson, Timothy B. Lowinger
Session Category: Experimental and Molecular Therapeutics
Session Date and Time: Sunday Apr 2, 2017 1:00 PM – 5:00 PM
Location: Convention Center, Halls A-C, Poster Section 26
Poster Board Number: 29
About XMT-1522
XMT-1522 incorporates a novel, proprietary HER2 antibody, which is conjugated with Mersana’s Dolaflexin platform which includes its Fleximer technology and proprietary auristatin payload. XMT-1522 provides a drug load of approximately 12-15 molecules per antibody, specifically designed to improve potency while simultaneously increasing tolerability. XMT-1522 has the potential to extend HER2-targeted therapy beyond the current "HER2-positive" populations into patients with lower levels of HER2 expression.
BeiGene Announces Initiation of First Pivotal Study in China with BTK Inhibitor BGB-3111
On March 2, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the dosing of the first patient in a pivotal clinical trial of BGB-3111, an investigational Bruton’s Tyrosine Kinase (BTK) inhibitor, in Chinese patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, BeiGene, MAR 2, 2017, View Source [SID1234517970]). BGB-3111 is also currently being evaluated in a global Phase III study in comparison with ibrutinib for the treatment of patients with Waldenström’s Macroglobulinemia. Schedule your 30 min Free 1stOncology Demo! "We are pleased to announce the beginning of the first pivotal clinical trial of BGB-3111 in China. BGB-3111 has been under clinical investigation since August 2014, and over 300 patients with various B-cell malignancies have been treated with BGB-3111 in Australia, New Zealand, the United States, Korea, and China," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman.
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"The initiation of the first pivotal trial in China with one of our portfolio compounds is an important step towards our goal of advancing innovative cancer treatments for patients in China," commented Lai Wang, Ph.D., Head of China Development.
The Phase II single-arm, open-label, multi-center study is designed to investigate the efficacy and safety of BGB-3111 in patients with relapsed or refractory MCL. The study’s primary endpoint is the objective response rate, defined as achievement of either a partial response or complete response at any time on study drug. Secondary endpoints include progression free survival, duration of response, time to response, safety, and tolerability. Professor Jun Zhu of the Beijing Cancer Hospital is the lead principal investigator of the trial.
About BGB-3111
BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK. BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib (the only BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase I experience, and sustained 24-hour BTK occupancy in both the blood and the lymph node.