On May 08, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported first quarter financial results (Press release, OncoMed, MAY 8, 2017, View Source [SID1234518968]). As of March 31, 2017, cash, and short-term investments totaled $156.9 million.

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"We continue to drive forward our strong immuno-oncology R&D pipeline, including anti-TIGIT, wholly-owned GITRL-Fc trimer, and our novel undisclosed immuno-oncology discovery programs — as well as advancing programs in our Celgene collaboration to $98 million in potential opt-in payments within the next two years," said Paul J. Hastings, OncoMed’s Chairman and CEO. "With more than two years cash, we are dedicated to advancing our pipeline while exploring partnering opportunities to advance all of our programs."

DENALI Phase 2 Clinical Trial Update

The company is reporting top-line results from the three arm randomized Phase 2 "DENALI" clinical trial of demcizumab (anti-DLL4, OMP-21M18) in combination with carboplatin and pemetrexed in front-line non-squamous non-small cell lung cancer (NSCLC). DENALI was designed to assess the efficacy and safety of either one or two 70 day truncated courses of demcizumab plus carboplatin and pemetrexed versus carboplatin and pemetrexed plus placebo. The primary endpoint of the study was overall response rate (ORR) and secondary endpoints were clinical benefit rate (CBR; rate of complete and partial responses and stable disease), progression-free survival (PFS), overall survival (OS) and safety. The statistical plan for DENALI was based on the expectation of enrolling 200 patients, but enrollment was discontinued at 82 patients due to the evolving treatment landscape in NSCLC. Of these 82 patients, 25 patients received carboplatin and pemetrexed plus placebo, while 57 received carboplatin, pemetrexed plus either one or two 70 day courses of demcizumab. Although these data were not fully mature at the time of analysis, demcizumab treatment failed to meet its efficacy endpoints when compared to placebo, with better outcomes apparent in the placebo group. Specifically, the ORR was 28% versus 52% (p=0.04) and CBR was 79% versus 92% (p=0.17) in the pooled demcizumab arms and the placebo arm, respectively. Median PFS was 5.5 months versus 8.7 months (p=0.02) and mOS was 15.5 months versus not reached (p=.06) in the pooled demcizumab arms and the placebo arm, respectively. No statistically significant differences in efficacy were observed between patients receiving one course or two courses of demcizumab. Demcizumab was generally well tolerated in combination with chemotherapy with nausea, fatigue, constipation, anemia and hypertension being the most common toxicities. There were no cases of Grade 3 or greater heart failure or pulmonary hypertension in this study. The overall safety profile was consistent with that observed in our other studies, and no new safety signals were identified.

OncoMed is discontinuing the dosing of all patients on the demcizumab trials, including the demcizumab plus pembrolizumab Phase 1b study, and will conduct a complete program review in the near term with its partner Celgene.

Recent Developments

Presented data from multiple preclinical studies detailing the mechanism and anti-tumor activity of anti-TIGIT alone and in combination with checkpoint inhibitors at the AACR (Free AACR Whitepaper) Annual Meeting 2017. The first patient in a Phase 1a single-agent study of OncoMed’s anti-TIGIT antibody (OMP-313M32) was recently enrolled.

Began enrollment of patients in two Phase 1b clinical trials of anti-DLL4/VEGF bispecific antibody (OMP-305B83), now known as navicixizumab, plus standard-of-care chemotherapy for the treatment of second-line colorectal and platinum-resistant ovarian cancers.

Announced partner Bayer Pharma decided not to exercise its option to license the first-in-class Wnt pathway inhibitors vantictumab (anti-Fzd, OMP-18R5) and ipafricept (Fzd8-Fc, OMP-54F28) for strategic reasons. OncoMed announced it put both programs on hold, and that it would pursue potential partnering opportunities for Wnt/IO combinations, utilizing different dosing regimens than those used in the Phase 1b studies. OncoMed has subsequently decided to cease dosing patients in the current vantictumab and ipafricept Phase 1b studies following a recent bone adverse event that occurred in a patient receiving vantictumab plus paclitaxel in the Phase 1b HER2-negative breast cancer trial.

Announced negative top-line trial results for YOSEMITE and PINNACLE Phase 2 studies and subsequent workforce reduction.

First Quarter 2017 Financial Results
Cash and short-term investments totaled $156.9 million as of March 31, 2017, compared to $184.6 million as of December 31, 2016.

Revenues for the first quarter 2017 totaled $6.2 million, as compared to $6.4 million in the first quarter of 2016. The slight decrease in revenue over the same period in 2016 was primarily due to slightly lower revenue recognized from reimbursement of research and development costs for services performed in the first quarter of 2017.

Research and development (R&D) expenses for the first quarter 2017 were $24.0 million compared with $28.4 million for the same period in 2016. The decrease was primarily due to lower external research and development costs attributable to the decrease in Phase 2 clinical trial costs of demcizumab and tarextumab programs, partially offset by an increase in internal program costs.

General and administrative (G&A) expenses for the quarter ended March 31, 2017 were $5.0 million, compared to $5.2 million for the same period in 2016. Decreased expenses during the first quarter 2017 were due to lower consulting and outside professional service costs.

Net loss for the first quarter 2017 was $22.6 million ($0.61 per share), compared to $27.2 million ($0.90 per share) for the same period of 2016. The change in net loss from the prior year quarter was due to lower R&D and G&A expenses.

2017 Financial Guidance
OncoMed anticipates 2017 full-year cash expenses will be approximately $90 million, including the impact of one-time severance-related charges in the range of approximately $2.6 million to approximately $3.1 million related to our previously announced workforce reduction. Based on the current plan, OncoMed anticipates that its current cash balance is sufficient to fund pipeline development and company operations through the third quarter of 2019, before considering potential opt-in milestones under our Celgene collaboration. These milestones include:

Anti-TIGIT: Potential $35 million following the completion of our ongoing Phase 1a clinical trial.

Rosmantuzumab (Anti-RSPO3): Potential $38 million following the completion of our ongoing Phase 1a and Phase 1b clinical trials, focused on RSPO3-high and RSPO gene fusion patients.

Navicixizumab (Anti-DLL4/VEGF): Potential $25 million following the completion of our ongoing Phase 1a and Phase 1b clinical trials.

Following potential opt-in, OncoMed would be eligible to co-develop and co-commercialize rosmantuzumab and/or navicixizumab with Celgene, while Celgene would assume all downstream costs and development activities for anti-TIGIT post option exercise. The company could be eligible to receive approximately $1.5 billion in downstream milestones related to these three programs, plus potential royalties and/or profit-sharing.

Conference Call Today
OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to review first quarter 2017 financial results and recent progress.

Analysts and investors can participate in the conference call by dialing 1-855-420-0692 (domestic) and 1-484-756-4194 (international) using the conference ID# 18252865. The webcast of the conference call can be accessed live on the Investor Relations section of the OncoMed website, View Source An audio replay of the conference call can be accessed by dialing 1-855-859-2056 (domestic) or 1-404-537-3406 (international) utilizing the conference ID number listed above. The web broadcast of the conference call will be available for replay through July 31, 2017 via the OncoMed website.

On May 8, 2017 /Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and SillaJen, Inc. (KOSDAQ: 215600) reported a new clinical and supply agreement for a Phase 1b dose-escalation study in renal cell carcinoma (RCC), or kidney cancer (Press release, Regeneron, MAY 8, 2017, View Source [SID1234518959]). The study will evaluate Regeneron’s PD-1 inhibitor, REGN2810, in combination with SillaJen’s oncolytic vaccinia virus, Pexa-Vec, in patients with previously treated metastatic or unresectable renal cell carcinoma.

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The open-label trial is expected to begin later this year, and is designed to evaulate the safety and efficacy of REGN2810 in combination with Pexa-Vec compared to treatment with REGN2810 as monotherapy. The study will initially open in Korea, with expansion to sites in the U.S.

Renal cell carcinoma is the most common type of kidney cancer in adults, and accounts for approximately three percent of adult malignancies and 90-95 percent of neoplasms arising from the kidney.

"We are pleased to announce this immuno-oncology agreement with Regeneron—another company doing groundbreaking work in oncology," said Eun Sang Moon, MD, DDS, Chief Executive Officer of SillaJen. "We believe that there may be synergies between our compounds and look forward to investigating this in our upcoming clinical trial in renal cell carcinoma."

Pexa-Vec has been shown to increase inflammation in the tumor micro-environment and potentially reverse the immunosuppressive microenvironment by activating T-cell mediated anti-tumor immune response. This may help "prime" the tumor by increasing sensitivity to anti-PD-1 treatment, such as REGN2810.

"Pairing our PD-1 inhibitor with other innovative approaches like Pexa-Vec allows us to evaluate multiple routes in the quest to provide important new treatments to people in need," Israel Lowy, MD, PhD, Vice President of Translation Sciences and Oncology, Regeneron. "Renal cell carcinoma is a devastating and currently under-treated disease, and combination therapies that enable the body’s immune response in novel ways may help improve these patients’ lives."

Under the terms of the agreement, the trial will be solely conducted and funded by SillaJen based upon a mutually developed study design," and Regeneron will provide REGN2810. Regeneron, in collaboration with Sanofi, is developing REGN2810 both alone and in combination with other therapies for the treatment of various cancers.

"Given the results reported thus far for monotherapy anti-PD1 immunotherapy and initial studies of Pexa-Vec for the treatment of advanced kidney cancer, we believe the combination of Pexa-Vec and REGN-2810 holds great promise," stated James Burke, MD, Chief Medical Officer of SillaJen. "This combination immunotherapy approach in RCC joins the oncolytic immunotherapy expertise of SillaJen with the well-known leadership of Regeneron in antibody targeted therapies."

About Pexa-Vec and the SOLVE Platform
Pexa-Vec is the most advanced product candidate from SillaJen’s proprietary SOLVE (Selective Oncolytic Vaccinia Engineering) platform. The vaccinia strain backbone of Pexa-Vec has been used safely in millions of people as part of a worldwide vaccination program, and over 300 cancer patients have been treated with Pexa-Vec to date. Pexa-Vec was engineered to target common genetic defects in cancer cells by deleting its thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration. Pexa-Vec is currently being evaluated in a worldwide Phase 3 clinical trial for advanced primary liver cancer, and more information can be found at View Source

About Regeneron Pharmaceuticals, Inc.
Regeneron (NASDAQ: REGN) is a leading science-based biopharmaceutical company that discovers, invents, develops, manufactures and commercializes medicines for the treatment of serious medical conditions. Regeneron commercializes medicines for eye diseases, high LDL-cholesterol, atopic dermatitis and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including rheumatoid arthritis, asthma, pain, cancer and infectious diseases. For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.

About SillaJen
SillaJen, Inc. (KOSDAQ: 215600) is a South Korean-based biotechnology company headquartered in Busan, South Korea, with satellite offices in Seoul, South Korea and San Francisco, CA. The company is focused on the development and commercialization of oncolytic immunotherapy products using the SOLVE platform, including its lead product Pexa-Vec, which is currently in Phase 3 trials for the treatment of advanced primary liver cancer. Additional information about SillaJen is available at www.sillajen.com.

On May 8, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported a clinical study agreement for a Phase 1b/2a immuno-oncology trial (Press release, Regeneron, MAY 8, 2017, View Source [SID1234518958]). The study will be conducted by Inovio in patients with newly-diagnosed glioblastoma multiforme (GBM) and will evaluate Regeneron’s PD-1 inhibitor, REGN2810, in combination with Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12.

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The open-label trial, which is expected to begin later this year, is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 patients. The study will be conducted at 30 U.S. sites and the primary endpoints are safety and tolerability. The study will also evaluate immunological impact, progression-free survival and overall survival.

GBM is a devastating disease for both patients and caregivers. It is the most aggressive brain cancer and its prognosis is extremely poor, despite a limited number of new therapies approved over the last ten years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than three percent.

"The unmet need for effective therapies in GBM remains extremely high. Certain immune checkpoint inhibitors have shown efficacy in certain cancers, but evidence increasingly suggests that the benefit of checkpoint inhibitors can be enhanced when used in combination with therapies that generate T cells," said David Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. "Inovio has an innovative immunotherapy platform which has shown the ability to generate antigen-specific T cells in disease areas including cancer. We look forward to exploring the potential of combining a T cell generating immunotherapy encoding multiple antigens with REGN2810, a PD-1 checkpoint inhibitor."

Under the terms of the agreement, the trial will be solely conducted and funded by Inovio, based upon a mutually agreed upon study design, and Regeneron will supply REGN2810. Inovio and Regeneron will jointly conduct immunological analyses in support of the study. Regeneron, in collaboration with Sanofi, is developing REGN2810 both alone and in combination with other therapies for the treatment of various cancers.

"Regeneron’s approach to oncology includes evaluating the combination of innovative therapies that act on diverse pathways and targets," said Israel Lowy, MD, PhD, Vice President of Translation Sciences and Oncology, Regeneron. "Using our PD-1 inhibitor as a therapeutic backbone alongside Inovio’s T cell-generating therapies offers a new path for exploration and heightens the potential to develop new, desperately-needed treatment options for patients."

"I am a strong believer in this combination regimen approach in immuno-oncology: use Inovio immunotherapies to generate killer T-cells to turn ‘cold’ tumors into ‘hot’ tumors, then block T cell suppression via checkpoint inhibition," said J. Joseph Kim, PhD, Inovio’s President and Chief Executive Officer. "This step with INO-5401 is very important for us in 2017, as we believe INO-5401 has the potential to be a powerful cancer immunotherapeutic in combination with promising checkpoint inhibitors such as Regeneron’s REGN2810, and we look forward to investigating its potential for GBM and multiple other challenging cancers."

About Glioblastoma
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most common and aggressive type of brain cancer. GBM is usually found in the area of the brain which controls some of the most advanced processes such as speech and emotions. GBM treatment is often limited by the tumor location and ability of a patient to tolerate surgery. Consequently, it is a particularly difficult cancer to treat. Worldwide there are an estimated 240,000 cases of brain and nervous system tumors per year; GBM is the most common and most lethal of these tumors.

About INO-5401
INO-5401 includes Inovio’s SynCon antigens for WT1, hTERT and PSMA and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted WT1, hTERT and PSMA among a list of attractive cancer antigens, designating them as high priorities for cancer immunotherapy development. WT1 was at the top of the list. The hTERT antigen relates to 85 percent of cancers, and WT1 and PSMA antigens are also widely prevalent in many cancers.

On May 8, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a highly potent pan-FLT3/BTK inhibitor, exerts compelling activity against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3 and eradicates AML tumors in a murine xenograft model (Press release, Aptose Biosciences, MAY 8, 2017, View Source;p=RssLanding&cat=news&id=2270752 [SID1234518895]). The data were presented in a poster on Sunday, May 7, 2017 at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference Hematologic Malignancies: Translating Discoveries to Novel Therapies, held May 6-9 in Boston, MA.

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The poster, entitled CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3, demonstrated the superior potency of CG’806, relative to competitive agents, against hematologic malignancy cell lines driven by various WT or mutant forms of FLT3. In addition, once daily oral dosing of CG’806 in a murine model achieved sustained micromolar plasma concentration over a 24hr period, and was accompanied by complete elimination of AML FLT3-ITD tumors in the absence of toxicity.
Results were presented by Weiguo Zhang, M.D., Ph.D., Assistant Professor of Leukemia at The University of Texas MD Anderson Cancer Center, for a research team led by Michael Andreeff, M.D., Ph.D., Professor of Leukemia.

"Given the potency of CG’806 against all of the mutant forms of FLT3 AML and the ability to eradicate AML tumors in murine xenograft models, CG’806 has demonstrated the potential to be superior to other FLT3 inhibitors and is beginning to differentiate itself as a targeted treatment for AML," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "We believe CG’806 has the potential to become the best-in-class FLT3 inhibitor, and our internal efforts now are focused on delivering CG’806 to AML patients as soon as practicable."

CG’806 and competitor FLT3 inhibitors were tested for potency to kill a series of isogenic cells, in which a specific form (WT or mutant) of FLT3 drove survival and proliferation of cells. Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with the ITD mutation, D835 mutations, the ITD plus F691I/Y842D/D835 mutations, or in FLT3 wild-type cells. The IC50s were 0.17, 0.82, 9.49, 0.30, 8.26, 9.72, and 0.43 nM for human FLT3-ITD mutated AML cells MV4-11 (FLT3-ITD) and MOLM13 (FLT3-ITD), murine leukemia Ba/F3 (FLT3-WT), Ba/F3 (FLT3-ITD), Ba/F3 (FLT3-D835Y), Ba/F3 (FLT3-ITD+D835Y), and Ba/F3 (FLT3-ITD+F691L) cells, respectively. CG’806 triggered profound apoptosis in cell lines harboring FLT3-ITD mutations and suppressed FLT3 and its downstream MAPK/AKT signaling. Moreover, CG’806 demonstrated in vivo tumor eradication without toxicity when administered orally, once daily for 14 days as a single agent in the MV4-11 AML murine xenograft model, and demonstrated sustained micromolar plasma drug levels in mice after a single oral administration.

The presentation will be published in the AACR (Free AACR Whitepaper) Hematologic Malignancies Conference Proceedings. The poster can also be accessed here or at the Publications & Presentations section of the Aptose website, www.aptose.com.

About CG’806
CG ‘806 is a once daily, oral, first-in-class pan-FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.