On April 1, 2019 Apollomics, Inc. (the "Company"), an innovative biopharmaceutical company committed to the discovery and development of oncology combination therapies, reported positive data for the Company’s multi-kinase inhibitor, APL-102, as both a single agent and in combination with an anti-PD-1 antibody in multiple preclinical studies (Press release, Apollomics, APR 1, 2019, View Source [SID1234534819]).

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"Our preclinical data presented today demonstrates a mechanism of action for APL-102 anti-tumor activity and a synergistic effect of the agent when combined with a check-point inhibitor (CPI)," said Sanjeev Redkar, PhD, President. "APL-102 treatment increased the total T-cells and the CD8 T-cells, and significantly decreased macrophages in the tumor, both as a single agent and in combination with an anti-PD1 antibody. We see a potential path forward for the agent as a single agent or in combination with CPIs which may improve the efficacy of APL-102 and broaden the efficacy of CPIs."

The studies, in multiple murine models, evaluated the effect of anticancer therapies that target components within the tumor microenvironment (TME) as opposed to the tumor itself. Colony stimulating factor 1 receptor (CSF-1R) was a key target as a means of controlling tumor associated macrophages in the TME. As a monotherapy, the results demonstrated that APL-102 inhibits CSF-1R in a radiometric enzyme activity assay with an IC50 of 43nM, and that APL-102 inhibited growth in cells dependent on CSF1-CSF1R signaling. APL-102 also demonstrated targeting of Vascular Endothelial Growth Factor Receptors (VEGFR) dependent angiogenesis and the Mitogen-Activated Protein Kinases (MAPK) pathway.

When APL-102 was given in combination with an anti-PD1 antibody, the results produced a more robust response than either single agent alone in syngeneic mouse models, which was associated with macrophage inhibition in the TME.

About APL-102

APL-102 is an oral, small molecule multi-kinase Inhibitor targeting several key oncogenic drivers. APL-102 inhibits both receptor tyrosine kinase (RTKs) and serine/threonine-kinases, including: angiogenesis via Vascular Endothelial Growth Factor Receptors (VEGFR) and Platelet-Derived Growth Factor Receptors (PDGFR); Mitogen-Activated Protein Kinases (MAPK) pathway via B-RAF and C-RAF; and, RET, CSF1R, DDR1 (discoidin domain receptor tyrosine kinase 1) and c-KIT. APL-102 is currently in preclinical, IND-enabling studies. The agent has demonstrated broad and potent antitumor activity in patient derived xenografts of liver cancer, breast cancer, colorectal cancer, gastric, esophageal and non-small cell lung cancer models with excellent oral bioavailability, biopharmaceutical properties, and a well-tolerated safety profile in a chronic safety study. Apollomics retains worldwide rights to APL-102.

On April 1, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported that its Phase 1/2 immuno-oncology trial in patients with newly diagnosed glioblastoma (GBM) has completed its enrollment three months ahead of schedule (Press release, Inovio, APR 1, 2019, View Source [SID1234534818]). The 52-patient trial is designed to evaluate Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens expressed by GBM and INO-9012, an immune activator encoding IL-12, in combination with cemiplimab-rwlc (also known as Libtayo or REGN2810), a PD-1 inhibitor developed by Regeneron Pharmaceuticals in collaboration with Sanofi. This trial information will be presented today at Phase I-III Trials in Progress session at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) being held in Atlanta.

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Inovio expects to report interim results from this study before the end of this year evaluating safety, immunological impact, progression-free survival and overall survival (see www.clinicaltrials.gov, identifier NCT03491683).

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "We sincerely thank the patients and their doctors for participating in our innovative combination trial. This is an important step for Inovio’s cancer combination strategy using our T cell-generating therapies in combination with PD-1/PD-L1 inhibitors for GBM and for multiple other cancers to improve overall efficacy of immunotherapy. We have previously shown in a Phase 1 head and neck cancer clinical study, combining Inovio’s T cell-generating immunotherapy MEDI0457 along with checkpoint inhibitors have resulted in two complete responders who remain cancer free for over two years. In this GBM trial, our goal is to increase the overall survival of patients facing a disease where neither the standard of care, nor clinical outcomes have changed in a clinically significant way in more than a decade."

Inovio holds clinical partnerships with AstraZeneca for MEDI0457 (in HPV-related cancers) and collaborations with Roche/Genentech and Regeneron for INO-5401 (in bladder cancer and GBM), each providing for clinical evaluation of Inovio immunotherapies combined with checkpoint inhibitors. In particular, the INO-5401 collaborations are based on a strong scientific rationale to combine two immunotherapies: INO-5401, which generates antigen-specific killer T cells, and a checkpoint inhibitor, which augments T cell activity.

About Glioblastoma

Glioblastoma (GBM) is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 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 five percent.

About INO-5401

INO-5401 includes Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens are known to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer.

On April 1, 2019 AstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for the MEK 1/2 inhibitor and potential new medicine selumetinib (Press release, AstraZeneca, APR 1, 2019, View Source [SID1234534817]).

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This designation is for the treatment of paediatric patients aged three years and older with neurofibromatosis type 1 (NF1) symptomatic and/or progressive, inoperable plexiform neurofibromas (PN), a rare, incurable genetic condition.

José Baselga, Executive Vice President, Research and Development, Oncology, said: "Selumetinib shows promise in the treatment of NF1-related plexiform neurofibromas, a rare and debilitating disease with no approved medications to date. The Breakthrough Therapy Designation acknowledges the significant unmet need of these patients and the potential benefit of selumetinib in this setting."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, at MSD Research Laboratories, said: "This new designation validates our ongoing development of selumetinib. As a result of this, selumetinib has the potential to receive expedited regulatory review and we hope to bring this medicine to patients as soon as possible."

The BTD is based on Phase II data from the SPRINT trial, testing selumetinib as an oral monotherapy in paediatric patients, aged three years or older with inoperable NF1-related PN. The results of the trial were presented by the National Cancer Institute (NCI) at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

This is the ninth BTD that AstraZeneca has received from the FDA since 2014. BTD is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results, which may demonstrate substantial improvement on a clinically-significant endpoint over available medicines.

Selumetinib was granted Orphan Drug Designation for the treatment of NF1 by the US FDA in February 2018 and the European Medicines Agency in August 2018.

Selumetinib is a MEK 1/2 inhibitor and potential new medicine licensed by AstraZeneca from Array BioPharma Inc. in 2003. AstraZeneca and MSD entered a co-development and co-commercialisation agreement for selumetinib in 2017.

The NF1 gene provides instructions for making a protein called neurofibromin, which negatively regulates the RAS/MAPK pathway, helping to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulations in RAS/RAF/MEK/ERK signalling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumour growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumour growth.

Selumetinib is being assessed as a monotherapy and in combination with other treatments in ongoing trials.

About SPRINT

The SPRINT trial is a US Cancer Therapy Evaluation Program (CTEP) NCI-sponsored Phase I/II trial. The Phase I trial was designed to identify the optimal Phase II dosing regimen, and the results were published in the New England Journal of Medicine.1

About NF1

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that affects one in 3,000 to 4,000 individuals.2,3 It is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas), skin pigmentation (so-called ‘cafe au lait’ spots) and, in 20-50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumours (MPNST).

People with NF1 may experience a number of complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. NF1 also increases a person’s risk of developing other cancers, including malignant brain tumours, MPNST and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.4

About the AstraZeneca and MSD Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza (olaparib), the world’s first PARP inhibitor and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

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 April 1, 2019 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported that the company will present at the H.C. Wainwright Global Life Sciences Conference in London on Monday, April 8, 2019 at 4:30 a.m. ET and the Needham Healthcare Conference in New York on Tuesday, April 9, 2019 at 2:50 p.m. ET (Press release, BioCryst Pharmaceuticals, APR 1, 2019, View Source [SID1234534816]).

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Links to a live audio webcast and replay of these presentations may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.

On April 1, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focusedon the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported its financial results for the year ended December 31, 2018 (Press release, Sutro Biopharma, APR 1, 2019, View Source [SID1234534813]).

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"This last year was a landmark one for Sutro. Our initial clinical trial for our first internal program, STRO-001 for the treatment of patients with multiple myeloma and non-Hodgkin’slymphoma, commenced in April 2018. Importantly, we also advanced our second clinical program, STRO-002 for the treatment of ovarian and endometrial cancers, to its clinical trial initiation in March 2019. On the business front, we entered a significant collaboration with Merck and completed our IPO in the second half of 2018," said Bill Newell, Sutro’s Chief Executive Officer. "In 2019, we look forward to the continued advancement of our internal programs, while working with our partners on progressing the collaboration product candidates."

Recent Business Highlights and Developments

STRO-001 Clinical Program

Potential first-in-class and best-in-class antibody-drug conjugate (ADC) directed against CD74, which is highly expressed in many B cell malignancies
Phase1 dose-escalation, with dose expansion, clinical trial enrolling patients with multiple myeloma and non-Hodgkin’slymphoma, with initial safety data expected to be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2019 and initial efficacy data expected by year end 2019
STRO-001 granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma
STRO-002 Clinical Program

Potential best-in-class ADC directed against folate receptor-alpha, which is highly expressed in ovarian cancer
Phase1 dose-escalation, with dose expansion, clinical trial enrolling women with advanced ovarian and endometrial cancers, with initial safety data expected by year end 2019
Corporate Highlights

Collaboration and licensing agreement with Merck signed in July 2018 to discover and develop novel immune-modulating therapies for cancer and autoimmune disorders
Initial public offering (IPO) that closed on October 1, 2018, provided Sutro with gross proceeds of $85.0 million, before deducting underwriting discounts and commissions and offering expenses. Additionally, Sutro received proceeds of $10.0 million from Merck in a private placement of common stock concurrent with the IPO
Full Year 2018 Financial Highlights

Cash, Cash Equivalents and Marketable Securities

As of December 31, 2018, Sutro had cash, cash equivalents and marketable securities of $204.5 million.

Revenue

Revenue was $38.4 million for the year ended December 31, 2018, which included collaboration revenue of $32.4 million recognized primarily from Celgene, Merck andEMD Serono, in addition to other revenue of $6.0 million. During the third and fourth quarters of 2018, Sutro began recording revenue from Merck, primarily from the $60.0 million upfront payment received by Sutro under the July 2018 collaboration and licensing agreement, which revenue will be recognized over multiple years. Future collaboration revenue from Celgene, Merck and EMD Serono, and from any future collaboration partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones and other collaboration agreement payments.

Operating Expenses

Total operating expenses for the year ended December 31, 2018, were $75.6 million compared with $71.0 million for the same period in 2017, including non-cash stock-based compensation of $2.9 million and $1.4 million, and depreciation and amortization expense of $4.5 million and $5.0 million, in the year 2018 and 2017, respectively. Total operating expenses for the year 2018 were comprised of research and development expenses of $54.3 million and general and administrative expenses of $21.4 million, with both expense types expected to increase in 2019 as Sutro’s internal product candidates advance in clinical development and additional general and administrative expenses are incurred as a public company following its IPO that closed on October 1, 2018.

Net Loss Per Share Calculation

Sutro financial statements following September 30, 2018, including share and per share amounts, give effect to common stock shares issued in the IPO and the Merck concurrent private placement, and common stock from the conversions of Sutro’s previously outstanding redeemable convertible preferred stock, as these transactions were completed on October 1, 2018.