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DelMar Pharmaceuticals Presents Positive Interim Data on VAL-083 Demonstrating Favorable Outcomes in Both Newly- Diagnosed and Recurrent GBM at the AACR Virtual Annual Meeting II

On June 22, 2020 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported positive interim data from its two Phase 2 trials of VAL-083 for the treatment of glioblastoma multiforme (GBM) demonstrating improved outcomes over current standard of care as both a first-line treatment and for recurrent GBM (Press release, DelMar Pharmaceuticals, JUN 22, 2020, View Source;diagnosed-and-recurrent-gbm-at-the-aacr-virtual-annual-meeting-ii [SID1234561324]). The data, presented in two posters at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, support the Company’s planned participation in the Global Coalition for Adaptive Research’s (GCAR) Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) clinical trial. DelMar previously announced its invitation from GCAR to participate in the selective GBM AGILE study. This pivotal study, with its robust trial design, industry leading partners, and strong regulatory endorsement, is intended to serve as the basis for VAL-083’s new drug application (NDA) submission and registration.

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Dr. John de Groot, Chairman of the Department of Oncology at MD Anderson Cancer Center and planned Principal Investigator for the VAL-083 arm of the GCAR GBM AGILE registration study, noted, "These data continue to demonstrate an improvement over the historical outcomes of standard therapy and validate VAL-083’s inclusion in a more robust setting as part of the GBM AGILE study. In MD Anderson’s Glioblastoma Moon Shots Program, we are looking to create giant leaps to help patients with GBM where treatment options are limited. It is our hope that VAL-083 may serve as an important new therapy to help physicians and patients dramatically reduce mortality and suffering due to this deadly cancer. We continue to be encouraged by these results and are excited by the opportunity to collaborate with DelMar and GCAR to further explore the potential of VAL-083."

Interim outcomes included:

Poster #CT273 – "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated glioblastoma"

Results:

For the 25 patients initially receiving the treatment dose that will be carried forward in the GBM AGILE pivotal study (30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle) median progression-free survival (PFS) was reported to be 8.7 months (confidence interval, or CI 6.0-12.0 months) as of the May 15, 2020 cut-off date.
Overall PFS (n=29) with VAL-083 was 8.7 months (CI 6.4-11.2 months).
While not a head-to-head trial, historically temozolomide (TMZ), the standard of care, has been demonstrated to have 6.9 months PFS in newly_diagnosed unmethylated GBM patients.
The open-label Phase 2 study in newly-diagnosed unmethylated GBM is being conducted at Sun Yat-sen University Cancer Center in China. The Company announced full enrollment of the study on February 19, 2020.

Poster #CT272 – "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated bevacizumab-naïve glioblastoma in the recurrent of adjuvant setting"

Results:

In recurrent GBM, for the 37 patients initially receiving the intended treatment dose that will be carried forward in the GBM AGILE pivotal study (30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle), median overall survival (mOS) is currently 8.5 months (CI 5.7-14.3 months) as of the May 28, 2020 cut-off date.
Overall mOS for the 72 patients who have completed at least one cycle of treatment was 7.1 months (CI 5.8-9.9 months).
While this is not a head-to-head trial, historically lomustine, which is the most commonly used chemotherapy for these patients, has demonstrated a mOS of 7.2 months in recurrent unmethylated GBM patients.
In the adjuvant setting, patients receive VAL-083 as adjuvant therapy following treatment with radiation and TMZ. As of the data cut-off date of May 28, 2020, 19 evaluable subjects have completed at least one 21-day cycle of treatment, with a total of 25 subjects enrolled. Enrollment for this arm was initiated in July 2019, and all 25 subjects enrolled to-date were alive at the data cut-off date.
Based on encouraging outcomes, the Company plans to increase the adjuvant arm from the originally planned 24 patients to include up to 12 additional patients.
The open-label Phase 2 study in recurrent and adjuvant unmethylated GBM is being conducted at M.D. Anderson Cancer Center in Houston.

Dr. Barbara O’Brien, Principal Investigator, commented, "These results continue to demonstrate the promise of VAL-083, along with a very favorable safety profile in both the adjuvant and recurrent settings. Further, we are excited to be able to add additional patients to the adjuvant arm of the study, which has received great interest from patients, and has enrolled faster than predicted. VAL-083 is well tolerated by these patients and extending the study provides an opportunity for patients to have access to this important trial for glioblastoma."

Similar to prior experience with VAL-083, myelosuppression has been the most common adverse event observed. Three subjects experienced a serious adverse event (SAE), possibly related to VAL-083 in the newly-diagnosed group, while 10 subjects have experienced a possibly drug-related SAE in the recurrent group, and one patient has experienced a possibly drug-related SAE in the adjuvant group as of the relevant data cut-off dates.

Saiid Zarrabian, CEO of DelMar Pharmaceuticals, added, "We continue to be encouraged with the interim outcomes for both of our ongoing Phase 2 trials of VAL-083 in GBM. With the support of these findings, we have commenced preparations for VAL-083’s participation in the GCAR pivotal GBM AGILE study. We look forward to reporting top-line results for the newly diagnosed Phase 2 study in the third quarter of 2020 and providing additional updates on both studies at the Society for Neuro-Oncology Annual Scientific Meeting in November 2020."

Ayala Pharmaceuticals Reports First Quarter 2020 Financial Results and Provides Business Update

On June 22, 2020 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported financial results for the first quarter ended March 31, 2020 and highlighted recent progress and upcoming milestones for its pipeline programs (Press release, Ayala Pharmaceuticals, JUN 22, 2020, View Source [SID1234561323]).

"Despite the challenges presented by the COVID-19 pandemic, Ayala continues to operate from a position of strength both clinically and operationally. We remain on track to report additional data from our ongoing Phase 2 ACCURACY study in R/M ACC and to initiate our Phase 2 AL101 study of TNBC before year end," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "In addition, in May 2020, we completed our upsized IPO, providing us the financial stability to further develop both AL101 and AL102 across a wide range of genetically defined cancer indications, as well as in multiple myeloma in collaboration with Novartis."

Key Business and Clinical Highlights

Completed Upsized Initial Public Offering: In May 2020, Ayala successfully completed its initial public offering (IPO) of 3,666,667 shares of common stock and additional 274,022 shares in connection with the partial exercise of the underwriters’ option to purchase additional shares, at a public offering price of $15.00 per share. The total gross proceeds from the IPO were approximately $59.1 million. Through this offering Ayala broadened its shareholder base with a number of U.S. healthcare dedicated funds.

Received Fast Track Designation for AL101 for the Treatment of Recurrent/Metastatic Adenoid Cystic Carcinoma (R/M ACC): In March 2020, Ayala received Fast Track designation from the U.S. Food and Drug Administration (FDA) for AL101 for the treatment of R/M ACC with Notch-activating mutations. Ayala’s lead product candidate, AL101 is a potent, selective, injectable small molecule gamma secretase inhibitor (GSI) and was granted Orphan Drug Designation in May 2019 for the treatment of R/M ACC.

Commenced Dosing of Patients in 6mg Cohort of R/M ACC Study: Ayala commenced dosing of the second patient cohort in its ACCURACY study for the treatment of R/M ACC with Notch-activating mutations at the higher dose of 6mg. In the first cohort of the study, 45 patients were dosed at 4mg where clear signs of clinical activity were observed along with a favorable safety profile. The study is expected to dose 42 patients in the 6mg cohort.

Investigational New Drug (IND) Accepted by FDA for Phase 2 Study of AL101 For Treatment of TNBC: In April 2020, the FDA accepted the IND for the Phase 2 study of AL101 for treatment of triple negative breast cancer (TNBC.) The FDA approved the dosing to commence at 6mg in a monotherapy study to evaluate TNBC patients bearing Notch activating mutations who have undergone 3 prior lines of therapies or less.

Upcoming Milestones

On Track to Report Additional Phase 2 Data of AL101 in Patients with R/M ACC Data in The Second Half of 2020: Ayala plans to report additional data from its ongoing Phase 2 ACCURACY study of AL101 for the treatment of patients with R/M ACC with Notch-activating mutations, a rare malignancy of the secretory glands, at an upcoming medical meeting in the second half of 2020. Initial data demonstrating a 15% response rate and 69% disease control rate were previously reported out of the first 39 evaluable patients in the 4mg cohort.

On Track to Initiate Phase 2 Study of AL101 in Patients with Recurrent/Metastatic Triple Negative Breast Cancer (R/M TNBC) in The Second Half of 2020: Ayala plans to initiate a Phase 2 clinical trial of AL101 for the treatment of patients with R/M TNBC with Notch-activating mutations in the second half of 2020, subject to the impact of COVID-19.

First Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents were $10.1 million as of March 31, 2020, as compared to $16.7 million as of December 31, 2019. Total cash, cash equivalents and marketable securities at March 31, 2020 did not include total net proceeds of approximately $55.0 million, after deducting underwriting discounts and commissions, from the Company’s IPO of 3,940,689 shares of common stock, including the partial exercise of the underwriters’ option to purchase additional shares, in May 2020. We expect the cash balance to fund operations into the second half of 2022 through potentially multiple key clinical and development milestones.

Collaboration Revenue: Collaboration revenue was $1.0 million for the first quarter of 2020, compared to $0.3 million for the same period in 2019. The increase in revenue was due to the advancement of our collaboration with Novartis on AL102 in combination with Novartis’ anti BCMA agent.

R&D Expenses: Research and development expenses were $5.1 million for the first quarter of 2020, compared to $2.8 million for the same period in 2019. The increase was primarily driven by higher costs related to the advancement of our ongoing Phase 2 study of AL101 in ACC and preparations for the initiation of the Phase 2 study in our TNBC trial.

G&A Expenses: General and administrative expenses were $1.3 million for the first quarter of 2020, compared to $0.8 million for the same period in 2019. The increase was primarily related to higher professional services and personnel costs to support the growth of the company.

Net Income/Loss: Net loss was $6.6 million, or $1.32 loss per share, for the first quarter of 2020, compared to $3.5 million, or $0.71 loss per share, for the same period in 2019, attributable mainly to the increase in our clinical operations.

Onconova Therapeutics Announces the Initiation of a Phase 1/2a Study of Rigosertib plus Nivolumab for the Treatment of KRAS+ Lung Adenocarcinoma

On June 22, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS) reported an investigator-initiated Phase 1/2a trial of oral rigosertib plus nivolumab in advanced metastatic KRAS mutated (KRAS+) lung adenocarcinoma has begun enrolling patients (Press release, Onconova, JUN 22, 2020, View Source [SID1234561322]).

"Over half of non-small cell lung cancers are classified as lung adenocarcinomas; of these, the largest subset has a KRAS mutation as the predominant genetic driver," said Dr. Steven Fruchtman, President and CEO, Onconova Therapeutics. "Despite discovering the KRAS mutation over 30 years ago, little progress has been made in KRAS+ directed treatments. The work under Dr. Rajwanth Veluswamy’s leadership at the Icahn School of Medicine is an important step towards determining if rigosertib, as a RAS-mimetic, can change that."

The investigator-initiated trial is an open-label, dose-escalating Phase 1 study followed by a Phase 2a dose-expansion phase to study the combination of oral rigosertib and nivolumab in metastatic KRAS+ lung adenocarcinoma patients who have progressed on standard frontline treatment. The study will assess safety and efficacy. Additional details are available on www.clinicaltrials.gov (NCT04263090).

"The novel combination of rigosertib with an anti-PD-1 antibody targets two of the most important oncogenic pathways in cancer biology," said Dr. Rajwanth Veluswamy, Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai. "This study will evaluate the safety and tolerability of this combination in KRAS mutated NSCLC in which patients have failed frontline immunotherapy. The study will explore efficacy of the combination in this common lung cancer subset and will also determine if rigosertib may restore sensitivity to the PD-1 blockade."

About Rigosertib

Rigosertib, Onconova’s lead candidate, is a proprietary Phase 3 small molecule. A key publication in a preclinical model reported rigosertib’s ability to block cellular signaling by targeting RAS effector pathways (Divakar, S.K., et al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling." Cell 165, 643). Onconova is currently in the clinical development stage with oral and IV rigosertib, including clinical trials studying single agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in HMA naive and refractory higher-risk MDS patients (Phase 2). Patents covering oral and injectable rigosertib have been issued in the US and are expected to provide coverage until at least 2037.

VBL Therapeutics Presents MOSPD2 Bi-Specific Antibody Activity and Potential Survival Benefit for Solid Tumors in Late Breaking Research Session of the AACR Virtual Annual Meeting

On June 22, 2020 VBL Therapeutics (Nasdaq: VBLT) reported a late-breaking study showing that its proprietary MOSPD2 bi-specific antibody candidates induced T-cell activation and significantly extended the survival of animals carrying established metastatic cervical and breast cancer (p=0.001; p=0.002) (Press release, VBL Therapeutics, JUN 22, 2020, View Source [SID1234561321]). Data are presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, being held June 22–24, 2020.

"Identifying a tumor-specific target is a key step for developing precise and safe immunotherapy for cancer, and MOSPD2 may be an ideal target. Our new data provide in-vitro and in-vivo proof-of-concept for the potential of VBL’s novel MOSPD2 bi-specific antibody candidates for immuno-oncology mediated therapy for solid tumors," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics.

VBL’s research has identified MOSPD2 as a protein involved in cell motility, whose expression is highly elevated in various solid tumors. The proprietary bi-specific antibody candidates developed by VBL have two separate arms – one arm binds to MOSPD2 on tumor cells and the second recruits host T-cells that attack the tumor. The data presented today demonstrate that the company’s bi-specific antibody candidates: 1) mediated killing of tumor cells by CD8 T-cells in a dose-dependent manner; 2) induced T-cell activation in-vivo; and 3) extended survival of tumor-bearing animals. The results highlight the potential of MOSPD2-mediated immuno-oncology therapy for the treatment of various solid tumors.

For VBL’s poster presentations at AACR (Free AACR Whitepaper) kindly see the following links: LB-poster and Poster2

About VBL’s VB-600 Platform
VBL is conducting two parallel drug development programs that are exploring the potential of MOSPD2 (motile sperm domain-containing protein 2), a protein that VBL has identified as a key regulator of cell motility, as a therapeutic target for inflammatory diseases and cancer. Our VB-600 platform comprises classical anti-MOSPD2 investigational monoclonal antibodies for inflammatory indications, as well as bi-specific antibody candidates for oncology.

Halozyme To Receive $10 Million Milestone Payment From Janssen

On June 22, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the company will receive a $10 million milestone payment from Janssen Biotech, Inc. (Janssen) triggered under the Collaboration and License Agreement between the two companies (Press release, Halozyme, JUN 22, 2020, View Source [SID1234561320]). The milestone payment is associated with the first commercial sale in the European Union of Janssen’s subcutaneous formulation of DARZALEX (daratumumab) utilizing ENHANZE, which was recently granted marketing authorization by the European Commission.