On January 3, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs in oncology, in particular against rare or resistant cancers, reported the identification of predictive biomarkers for AsiDNA, its first-in-class non-targeted DNA Damage Response (DDR) inhibitor, which enables personalized medicine approaches (Press release, Onxeo, JAN 3, 2019, View Source [SID1234532449]).

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Judith Greciet, Chief Executive Officer of Onxeo, said: "The development of AsiDNA is undergoing a strong momentum both in terms of preclinical and clinical activities. Identifying predictive biomarkers is an important step forward that will assist in the design of the next phases of the clinical development of AsiDNA. Indeed, these biomarkers will make possible an upstream selection of the patients with a better sensitivity to treatment with AsiDNA, which will maximize the likelihood of success for upcoming clinical studies as well as enable a personalized medicine approach for these patients over time. We now have a robust and state-of-the-art set of preclinical and clinical data for this particularly promising drug candidate in the field of DDR. The identified biomarkers are important components in the design of future studies and will be included as soon as the next phase 1b/2 combination study that we expect to initiate in the coming weeks, thanks to the favorable intermediate results of activity and tolerance in the ongoing DRIIV-1 study. Each of these advances in our developments significantly enhances the value of AsiDNA and our R&D assets."

Preclinical studies identified predictive biomarkers for patient selection in upcoming studies of AsiDNA

Extensive tests investigated AsiDNA sensitivity signature using bioinformatics analysis from transcriptomic experiments, validated this signature in vitro on multiple cell lines and then analyzed the genes presenting an expression profile highly correlated with sensitivity to AsiDNA.

These studies showed that sensitivity to AsiDNA is correlated with the level of DNA repair gene expression in the tumor and identified several tumor genes for which the level of expression is the most correlated to AsiDNA sensitivity. A low level of these genes expression in a patient’s tumor greatly increases the likelihood that the patient will respond to treatment with AsiDNA. As a result, analysis of these genes will be used to select the patients with the highest sensitivity to treatment and thus the greater probability of response in upcoming trials.

Use of such predictive biomarkers is part of the best practices in clinical trial design and in treatment (personalized medicine) today. During clinical development, their use greatly reduces risks and maximizes the chances of success. In clinical practice, prior assessment via predictive biomarkers allows for personalized care that optimizes the patient’s chances by selecting the most appropriate treatment for a given patient.

On January 3, 2019 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported status updates highlighting progress with the Company’s key programs (Press release, Replimune, JAN 3, 2019, View Source [SID1234532398]).

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"Replimune had a very productive 2018 with our successful initial public offering in July providing us with the funds to continue to advance our new generation of potentially best in class oncolytic immuno-gene therapies into and through clinical trials," said Robert Coffin, Ph.D., co-founder, President and CEO of Replimune. "We have made tremendous progress with all aspects of our business and are pleased that all programs continue to progress on track. We now look forward to 2019 when we expect to initiate enrollment of the Phase 2 portion of the Phase 1/2 clinical trial of RP1 in combination with nivolumab in four solid tumor types, initiate enrollment of our potentially pivotal randomized controlled Phase 2 clinical trial of RP1 in combination with cemiplimab in cutaneous squamous cell carcinoma (CSCC), and initiate clinical development of our RP2 product candidate expressing anti-CTLA-4."

Program Updates

RP1:RP1 is Replimune’s first product candidate to enter the clinic and is based on a proprietary new strain of herpes simplex virus armed with a gene encoding a potent fusogenic protein (GALV-GP-R-), intended to enhance tumor killing potency, immunogenic cell death and the activation of systemic anti-tumor immune responses, and with a gene encoding the cytokine GM-CSF. Replimune is currently testing RP1 in a two-part Phase 1/2 clinical trial in collaboration with Bristol Myers Squibb. In part one of the Phase 1/2 clinical trial, Replimune is assessing the safety and tolerability of RP1 administered alone in patients with advanced solid tumors followed by dosing in combination with nivolumab anti-PD1 therapy. In part two of the Phase 1/2 clinical trial Replimune intends to study the safety and efficacy of RP1 in combination with nivolumab in four cohorts of patients with different solid tumor types. Replimune also intends to initiate a registration-directed randomized controlled Phase 2 clinical trial of approximately 240 patients with CSCC comparing treatment with cemiplimab alone to treatment in combination with RP1, under the Company’s collaboration with Regeneron. Cemiplimab is Regeneron’s anti-PD1 drug which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of locally recurrent and metastatic CSCC in 2018.
Recent RP1-specific program progress is summarized below:

Completed enrollment of RP1 alone in the Phase 1 portion of the Phase 1/2 study.
Opened enrollment of the second part of the Phase 1 portion of the study, in which RP1 is being combined with nivolumab, in the United States (U.S.) and United Kingdom (UK).
Data from the full Phase 1 part of the Phase 1/2 study (RP1 alone and RP1 combined with nivolumab) is expected to be presented at a medical conference in the second half of 2019.
On track to initiate the Phase 2 portion of the study in the first half of 2019 in four cohorts of approximately 30 patients each with melanoma, bladder cancer, microsatellite instability high cancers, and non-melanoma skin cancers.
On track to initiate the registration-directed randomized, controlled Phase 2 clinical trial of RP1 in combination with cemiplimab in CSCC in the first half of 2019.
Pipeline product candidates (RP2 & RP3)

Replimune’s pipeline product candidates are further armed versions of RP1 which focus on the delivery of immune activating genes to tumors which target clinically validated pathways that act as the immune response is initiated. In particular, these are pathways where Replimune believes systemic engagement may be sub-optimal.

RP2 is a version of RP1 that, in addition to expressing GALV-GP-R and GM-CSF, also expresses a genetically encoded anti-CTLA-4 antibody intended to block the inhibition of the initiation of immune response caused by CTLA-4. RP2 is intended to be used primarily in combination with anti-PD-1 or anti-PD-L1 therapy.
The Company remains on track to initiate the clinical development of RP2 in a Phase 1 clinical trial of RP2 alone and in combination with anti-PD1 therapy in the first half of 2019.
RP3 is a further armed oncolytic immuno-gene therapy which expresses two immune co-stimulatory activating ligands. Following the assessment of a number of co-stimulatory pathways, which like anti-CTLA-4 are expected to be primarily active at the site and time of anti-tumor immune response initiation, the selected RP3 product candidate to be moved forward to clinical development has now been finalized and will express CD40L and 4-1BBL, together with anti-CTLA-4 and GALV-GP-R-. CD40L activates CD40, resulting in the broad activation of both innate and adaptive immunity, and 4-1BBL activates 4-1BB (CD137) to promote the expansion of cellular and memory immune responses.
The Company remains on track to initiate the clinical development of RP3 in a Phase 1 clinical trial of RP3 alone and in combination with anti-PD1 therapy in the first half of 2020.
Cash Position: Based on its current operating plan, Replimune expects that its current cash, cash equivalents and short-term investments will enable it to fund its operating expenses and capital expenditure requirements into the second half of 2021.

JPMorgan Conference Presentation and Webcast

As previously announced, Replimune will be presenting at the 37th Annual JPMorgan Healthcare Conference on January 9 at 8:00am PT.

A simultaneous webcast will be available in the Investors section of Replimune’s website at www.replimune.com. A replay will be available for 30 days following the conference.

On January 3, 2019 Peloton Therapeutics, Inc., a clinical-stage pharmaceutical company advancing first-in-class oral medicines for cancer and other serious conditions, reported that it will be presenting at the 37th Annual J.P. Morgan Healthcare Conference (Press release, Peloton Therapeutics, JAN 3, 2019, View Source [SID1234532415]). John A. Josey, Ph.D., Chief Executive Officer, will present at 3:30 p.m. PDT on Tuesday, January 8, 2019 at the Westin St. Francis in San Francisco, California.

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On January 3, 2019 GT Medical Technologies, Inc., a company dedicated to improving the lives of patients with brain tumors, reported positive results from a clinical trial supporting the efficacy and safety profile of a new treatment, GammaTile Therapy, for patients with recurrent, previously treated brain tumors known as meningiomas (Press release, GT Medical Technologies, JAN 3, 2019, View Source [SID1234532431]). Meningiomas are the most common type of primary brain tumor. They are usually non-cancerous but can have a significant impact on patients’ lives, causing headaches, seizures, cognitive decline, and other life-threatening symptoms. Results were published in the Journal of Neurosurgery (JNS), the official journal of the American Association of Neurological Surgeons.

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In this single-arm, prospective study, 20 recurrent meningiomas were treated with adjuvant GammaTile Therapy immediately following surgery. The study found that in patients undergoing surgery followed by GammaTile, there was a statistically significant improvement in time-to-local disease progression (TTP) compared to the same patients’ prior rounds of treatment. At the time of the analysis, median TTP for tumors treated with GammaTile had not been reached because less than half of the patients had experienced tumor recurrence. Median TTP for tumors treated with GammaTile is projected to be at least 29 months (95 percent confidence interval) – nearly a year longer than results for prior rounds of treatment (18.3 months TTP, HR=0.17, p=0.02). At 18 months post-treatment, tumors had not recurred in 89 percent of patients treated with GammaTile, compared to 50 percent for prior rounds of treatment without GammaTile. Treatment with GammaTile was well tolerated.

GammaTile is an FDA-cleared, surgically targeted radiation therapy (STaRT) for patients with recurrent intracranial neoplasms (brain tumors) including primary (benign or malignant) and metastatic tumors. Placed directly at the site of the tumor cavity during the last few minutes of excision surgery, GammaTile Therapy is a new approach that immediately begins targeting residual tumor cells, before they can replicate. Designed to help protect healthy brain tissue and facilitate rapid, accurate placement during the procedure, the therapy features a bioresorbable, conformable, 3D-collagen tile and uniform radiation source.

GammaTile Therapy offers advantages over the most common treatment for patients undergoing surgery for recurrent brain tumors: a course of External Beam Radiation Therapy (EBRT), which requires daily treatments for up to six weeks. Some patients may not be candidates for EBRT. Once the disease has returned, many people with recurrent brain tumors have already received levels of radiation therapy that make the risk of additional external beam radiation outweigh the potential benefits. Additionally, those patients who are potentially candidates for EBRT typically have to wait two weeks or more for surgical wound healing before beginning treatment, giving any residual tumor cells a chance to replicate.

"In patients with recurrent meningiomas, treatment options are extremely limited. Repeat surgery may not be a good option without an effective adjuvant therapy. With GammaTile, we can now offer patients who otherwise would not have been able to receive treatment or who would likely be facing early recurrence another option – one proven to delay local meningioma tumor progression out to two years," said Peter Nakaji, M.D., co-author of the study and GT MedTech’s co-founder and director of the Neurosurgery Residency Program at Barrow Neurological Institute. "Because it is delivered directly to the tumor bed, GammaTile offers the benefits of radiation while minimizing damage to surrounding healthy tissue from EBRT, and reduces the need for patients to return for daily outpatient radiation treatments."

Because the therapy is implanted at surgery, patients treated with GammaTile Therapy require no additional trips to the hospital or clinic for radiation therapy. The therapy is targeted, so patients receive radiation only where it is needed and may receive a lower overall level of exposure of normal tissue to radiation. GammaTile Therapy can emit two-and-a-half times the radiation dose compared to the dose that can be achieved from EBRT. This dose is delivered to a localized area and is highly lethal to residual tumor cells.

Approximately 400,000 Americans are newly diagnosed with some type of brain tumor each year.1 Despite the efforts of the most skilled brain tumor specialists throughout the world, outcomes for patients with brain tumors have improved little over the past 30 years. Recurrence of brain tumors is common, and about half of all patients treated for brain tumors have their disease recur within a year.

"As a treating physician, I have seen first-hand the need for better options for our patients. We created GammaTile as a therapy designed to be immediate, safe, predictable, and effective," said GT MedTech’s co-founder and chief technology officer David G. Brachman, M.D., lead author of the study, who previously served as chairman and medical director of Radiation Oncology at St. Joseph’s Hospital and Barrow Neurological Institute in Phoenix, Ariz. "These first published clinical data on the technology demonstrate that GammaTile is an effective therapy option that significantly delays the progression of this common brain tumor type."

GammaTile Therapy received FDA 510(k) regulatory clearance for the treatment of all types of recurrent brain tumors in July 2018. The data published in JNS are the initial results of a larger basket-design study that looked at the use of GammaTile in 108 patients with several kinds of recurrent brain tumors, including gliomas and brain metastasis.

Dr. Brachman continued, "We are encouraged by these data in meningiomas and look forward to sharing data on the use of this treatment in other aggressive brain tumor types in the near future."

On January 3, 2019 Avalon GloboCare Corp. (NASDAQ: AVCO), a leading global developer of cell-based technologies, reported that the Company and its wholly owned subsidiary, Avactis Biosciences, have entered into a joint venture and exclusive license agreement with Arbele Limited to co-develop next generation, transposon-based Chimeric Antigen Receptor (CAR)-T and CAR-Natural Killer (NK) cellular therapies (Press release, Avalon, JAN 3, 2019, View Source [SID1234609548]). These unique CAR vector constructs are non-virally engineered, possessing multiple therapeutic targets as well as unique "safety-switch" mechanisms. Based on Avalon’s extensive hospital network for cellular therapy, together with the Company’s established GMP bio-production facility in China (Epicon Biotech, Nanjing), this joint venture allows Avalon to accelerate the clinical development of more efficacious and safer CAR-T/CAR-NK therapies, such as those developed by Arbele.

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"We are very excited to establish this joint venture with Arbele Limited to accelerate our clinical programs in cellular therapy," stated David Jin, M.D., Ph.D., CEO and President of Avalon GloboCare Corp. "Arbele’s strong proprietary technology platform in designing and production of non-viral, transposon-engineered, multi-targeted CAR will allow us to generate next-generation, better and safer CAR-T and CAR-NK cellular therapeutics. This joint venture will strengthen our core technological capabilities, enrich our intellectual properties, as well as further establish our leadership in the field of cellular immunotherapy," added Dr. Jin.