On March 26, 2018 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring an NTRK gene fusion (Press release, Loxo Oncology, MAR 26, 2018, View Source [SID1234524992]).

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"We are grateful to the many patients who participated in our clinical trials in the spirit of helping others with advanced cancer," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We hope that the larotrectinib development program inspires others to develop drugs for both adult and pediatric patients on the basis of tumor genetics rather than tumor site of origin."

Loxo Oncology and Bayer are engaged in a collaboration for the development and commercialization of larotrectinib. A Marketing Authorisation Application (MAA) submission by Bayer in the European Union is expected in 2018.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and highly selective tropomyosin receptor kinase (TRK) inhibitor. The investigational new drug is in clinical development for the treatment of patients with cancers that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In clinical trials, larotrectinib demonstrated marked and durable anti-tumor activity in TRK fusion cancer regardless of patient age or tumor type. In an analysis of 55 RECIST-evaluable adult and pediatric patients with NTRK gene fusions, larotrectinib demonstrated an 80 percent investigator-assessed confirmed overall response rate (ORR) and a 75 percent centrally-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib was well tolerated; the majority of all adverse events were grade 1 or 2. There were no treatment-related grade 4 or 5 events, and no treatment-related grade 3 adverse events occurred in more than 5% of patients.

Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA.

In November 2017, Loxo Oncology and Bayer entered into an exclusive global collaboration for the development and commercialization of larotrectinib and LOXO-195, a next-generation TRK inhibitor. Bayer and Loxo Oncology will jointly develop the two products with Loxo Oncology leading the ongoing clinical studies as well as the filing in the U.S., and Bayer leading ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About TRK Fusion Cancer
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled tropomyosin receptor kinase (TRK) signaling that can lead to cancer. NTRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. NTRK gene fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH) or immunohistochemistry (IHC), to detect TRK protein. For more information, please visit www.trkcancer.com.

On March 26, 2018 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported 2 year recurrence rate data from the Phase 2 trial evaluating HS-410 (vesigenurtacel-L) in combination with standard of care, Bacillus Calmette-Guérin (BCG), for the treatment of non-muscle invasive bladder cancer (NMIBC) (Press release, Heat Biologics, MAR 26, 2018, View Source [SID1234524990]). As previously announced, the Company discontinued its HS-410 program in order to focus its resources on current and future checkpoint combination trials, including its HS-110 Phase 2 lung cancer program in combination with Bristol-Myers Squibb’s checkpoint inhibitor nivolumab. However, in keeping with clinical trial guidance, Heat continued to monitor all patients enrolled in the study for a 2-year duration.

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Within the subgroup of patients who received the low dose of Heat’s ImPACT HS-410 with standard of care BCG and who demonstrated a positive immune response, 10 out of 10 (100%) remained disease-free after a 2-year period. A positive immune response was defined as 2-fold or greater increase from baseline of CD8+ T cells in peripheral blood as measured by ELISPOT analysis.

Jeff Wolf, Heat’s CEO, commented, "We are further encouraged by this latest data in immune responders showing a 100% disease-free survival rate over 2 years, in the subgroup of patients that received low-dose HS-410 and BCG. The observed clinical benefit is consistent with our recent data in non-small cell lung cancer where we reported that patients who have robust immune responses as measured by ELISPOT analysis, have improved survival benefit, providing further support for the mechanism of action of our unique gp96-based T-cell Activation Platform. Heat is committed to the development of its therapeutic programs in combination with a PD-1/PD-L1 inhibitor, as we believe this provides us the best opportunity for a sustained, activated CD8+ T-cell response."

Jeff Hutchins, Heat’s Chief Scientific Officer, further commented, "We believe the future of immuno-oncology therapy will be built on a multipronged, orchestrated attack: polyclonal T-cell activation, clonal T-cell expansion and checkpoint inhibition. Most importantly, we believe the ability to mount a robust poly T-cell activated immune response has the potential to improve clinical outcomes. We are encouraged by the correlation of clinical benefit and immune responses linked to our gp96-based poly-neoantigen T-cell activation platform in these two different cancer settings."

Heat recently reported positive interim results from its Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), in patients with advanced non-small cell lung cancer (NSCLC).

Ablynx has filed a 20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 20-F, Ablynx, 2018, MAR 26, 2018, View Source [SID1234524997]).

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On March 24, 2018 Barricade Therapeutics reported a study conducted at The Wistar Institute in collaboration with The University of Texas Southwestern Medical Center which has demonstrated the efficacy of targeting aberrantly active telomerase to treat therapy-resistant melanoma (Press release, Barricade Therapeutics, MAR 24, 2018, View Source [SID1234524977]).

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A hallmark of several cancer types, including melanoma, is increased telomerase activation. Telomerase is an enzyme responsible for elongating telomeres which protect the integrity of chromosome ends during cell replication. While absent in most normal cells, telomerase is highly active in cancer cells, driving continuous cell divisions.

"Telomerase is an almost universal oncology target. In the present study, we provide a scientific rationale for the development of new clinical cancer treatments based on targeting telomeres in cancer cells," said Jerry W. Shay, co-author of the study, and professor of Cell Biology at UT Southwestern Medical Center.

Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma Research and director of The Wistar Institute Melanoma Research Center, and his collaborators used a modified telomerase substrate they had previously described, 6-thio-2’-deoxyguanosine or 6-thio-dG (THIO), to utilize telomerase to induce telomere dysfunction. They demonstrated that THIO induced cell death in melanoma cells harboring BRAF gene mutations and impaired tumor growth in several BRAF-mutant mouse melanoma models without affecting the viability of normal skin cells.

The team also studied the ability of THIO treatment to stop proliferation and tumor growth of therapy-resistant melanoma cells. They created a large panel of human melanoma cell lines with acquired resistance to targeted therapy and immunotherapy and showed a general sensitivity of these cells to THIO both in vitro and in vivo.

"These exciting results add to a substantial amount of scientific data on THIO supporting our development program," said Frank Perabo, CEO of Barricade Therapeutics. "The data suggest that THIO could be studied in future clinical trials in a first- and second-line therapy setting, or in combination with other agents to overcome intrinsic resistance."

This work was supported by grants from NIH, DoD, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Melanoma Research Foundation

On March 24, 2018 -ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported encouraging efficacy and favorable tolerability data from the FORWARD II cohort assessing mirvetuximab soravtansine in combination with Merck’s anti-PD-1 therapy pembrolizumab in patients with platinum-resistant epithelial ovarian cancer (EOC) (Press release, , 24 24, 2018, View Source [SID1234524978]). These data are being presented at the Society of Gynecologic Oncology (SGO) Annual Meeting, March 24-27, 2018 in New Orleans, LA.

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"Initial safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in platinum-resistant epithelial ovarian cancer (EOC) patients"

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Key findings in 14 heavily pre-treated patients are as follows:

In the subset of 8 patients with medium or high folate receptor alpha (FRα) expression levels, the confirmed overall response rate (ORR) was 63 percent (95% CI 25, 92), with a median progression-free survival (PFS) of 8.6 months (95% CI 1.6, upper bound not yet reached).
For all patients, the confirmed ORR was 43 percent (95% CI 18, 71), with a median PFS of 5.2 months (95% CI 1.6, 9.5); patients in this cohort had received a median of 4.5 prior lines of systemic therapy, with 64% of patients receiving 4 or more prior lines.
As previously reported, at full dosing, the combination of mirvetuximab (6 mg/kg) and pembrolizumab (200 mg, supplied by Merck) demonstrates favorable tolerability, consistent with the known safety profiles of each agent, with primarily mild to moderate (≤ grade 2) adverse events observed.
Based on these data, ImmunoGen is enrolling an additional 35 patients with medium or high FRα expression levels in an expansion cohort in the FORWARD II study.

"We are encouraged by the early evidence of anti-tumor activity with durable responses and the tolerability profile of mirvetuximab in combination with pembrolizumab, particularly among the subset of patients with medium or high folate receptor alpha expression where we saw the greatest benefit," said Anna Berkenblit, M.D., Vice President and Chief Medical Officer of ImmunoGen. "Across multiple combinations, we’ve demonstrated that our Phase 3 single agent dose level for mirvetuximab combines readily with other therapies. The consistency of these findings further underscore the potential of mirvetuximab for ovarian cancer – both as monotherapy, and in combination with other therapies in earlier lines of treatment."

Featured Poster Presentation Details

Title: "Initial safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in platinum-resistant epithelial ovarian cancer (EOC) patients" (abstract #74)

Lead author: Ursula Matulonis, M.D., Director and Program Leader, Gynecologic Oncology Program, Dana-Farber Cancer Institute, Boston, MA

The findings will be presented during featured poster presentation discussion sessions:

Sunday, March 25 at 3:30pm CT
Monday, March 26 at 3:30pm CT
Additional information can be found at www.sgo.org

About FORWARD II
FORWARD II is a Phase 1b/2 study of mirvetuximab in combination with Avastin (bevacizumab), pegylated liposomal doxorubicin, or Keytruda (pembrolizumab) in patients with FRα-positive platinum-resistant EOC, primary peritoneal, or fallopian tube tumors, as well as a doublet combination of mirvetuximab with carboplatin and a triplet combination of mirvetuximab plus carboplatin and Avastin in patients with platinum-sensitive ovarian cancer.

About Mirvetuximab Soravtansine
Mirvetuximab soravtansine (IMGN853) is the first FRα-targeting ADC. It uses a FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.