On November 29, 2021 Tetra Bio-Pharma Inc. ("Tetra" or the "Company") (TSX: TBP) (OTCQB: TBPMF) (FRA: JAM1), a leader in cannabinoid-derived drug discovery and development reported positive initial clinical data from its ongoing Phase 2 clinical trials (REBORN©1 and PLENITUDE©) of QIXLEEF for cancer pain (Press release, Tetra Bio Pharma, NOV 29, 2021, View Source [SID1234596226]). QIXLEEF is a botanical inhaled investigational new drug with a fixed ratio of THC and CBD that meets USA cGMP regulatory requirements.

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The REBORN©1 trial is a head-to-head, open-label, crossover phase 2 study against oral opioids in the management of short and frequent episodes of incapacitating pain (breakthrough pain) in patients with cancer. The REBORN©1 study protocol is assessing the safety and preliminary efficacy of QIXLEEF in onset of pain relief and on pain intensity compared to three types of immediate release oral opioids: oral morphine sulfate immediate release, oral hydromorphone immediate release, and oral oxycodone immediate release. The PLENITUDE© trial is a randomized double-blind phase 2 study assessing the safety and efficacy of QIXLEEF in patients with cancer who have uncontrolled pain. Both studies are conducted across multiple clinical sites located in the United States.

Safety data of the REBORN©1 trial collected up to now confirm QIXLEEF tolerability and good safety profile in patients with cancer with breakthrough pain; no serious adverse events have been reported, only adverse drug reactions of mild intensity have been recorded. Preliminary data of the PLENITUDE© trial also confirm QIXLEEF tolerability and good safety profile in the pool of subjects treated with either QIXLEEF or the placebo in the randomized double-blind 4-week period and in subjects treated with QIXLEEF during the open-label 11-month period. Preliminary analysis of the data shows a positive effect on pain relief in QIXLEEFTM-treated patients. The Company cannot disclose further data on efficacy due to regulatory compliance.

Dr. Guy Chamberland, CEO and CRO commented, "A safe and efficient therapeutic alternative that allows the reduction of opioids is critical now more than ever to support patients in their journey against pain. Preliminary data from both REBORN©1 and PLENITUDE© confirm the safety and pharmacodynamic profile of QIXLEEF reported in the phase I trials. The pharmacokinetic profile of QIXLEEF is well indicated to help manage short episodes of pain such as breakthrough pain and will offer patients and physicians a viable, safer, and non-opioid option for pain management."

Lastly, Tetra’s metabolite profile study in humans showed that intake of QIXLEEF does not lead to significant levels of metabolites associated with toxicity and its pharmacokinetic profile mirrors the temporal characteristics of breakthrough cancer pain episodes, with a transient and fast effect of action. Tetra’s Phase I trials showed that maximal plasma concentration was reached within 5 minutes and that the drug was well tolerated with a good safety profile.

About Breakthrough Cancer Pain

Opioids are the cornerstone of the management of cancer pain. The opioid crisis is serious, and the number of deaths related to overdosing remains elevated (Opioid Basics | CDC’s Response to the Opioid Overdose Epidemic | CDC). Tetra’s cannabis and cannabinoid-derived product pipeline has the potential to play a significant role in opioid use reduction, thus addressing a societal issue of critical proportion.

Current opioids approach to manage breakthrough pain are inadequate to timely relieve pain in patients with cancer. Immediate-release oral morphine produces an analgesic effect in 30-45 minutes, with peak effect at ~1 hour or more (Staahl C. et al., Journal of Clinical Pharmacology, 2008; 48:619-631), in contrast to episodes of breakthrough cancer pain, which typically peak within 3-15 minutes and last ~1 hour. In addition to inappropriate time window of efficacy, immediate-release oral opioids affect the patient’s functioning (e.g., confusion) and quality of life (e.g., constipation, drowsiness, sleep disorders) and may induce life-threatening side effects such as respiratory depression in addition to multiple side effects. More potent opioids such as fast-onset opioids have a higher risk of abuse potential, increasing the risk of misuse and overdose. There is currently no therapeutic solution that offers fast onset of pain relief with an acceptable safety profile and low risk of abuse potential.

On November 29, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to proceed with a Phase 1b/2 clinical trial of its anti-CTLA-4 monoclonal antibody (mAb), ADG116, in combination with the anti-PD-1 antibody, pembrolizumab (Press release, Adagene, NOV 29, 2021, View Source [SID1234596225]). The global trial (ADG116-P001 / KEYNOTE-C97) will evaluate patients with advanced/metastatic solid tumors at multiple sites in the U.S. and Asia Pacific (APAC).

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ADG116 utilizes Adagene’s proprietary NEObody platform technology and is designed to target a unique conserved epitope of CTLA-4 with enhanced efficacy by potent Treg depletion in the tumor microenvironment (TME). ADG116 is designed with a soft ligand blocking to address safety concerns associated with existing CTLA-4 therapeutics.

"The FDA clearance of this trial represents a significant milestone for our anti-CTLA-4 program as we advance our evaluation of ADG116 in combination with anti-PD-1 therapy," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "By applying NEObody technology, ADG116 can overcome existing safety limitations of anti-CTLA-4 therapies to achieve improved clinical benefit. Our exploration of ADG116 with pembrolizumab aims to unleash the dual CTLA-4/PD-1 blockade and realize the full potential of this combination therapy approach as a cornerstone of cancer treatment – balancing safety and efficacy."

The ADG116-P001 trial is expected to dose the first patient in early 2022, and is designed to evaluate the safety and tolerability, determine the maximum tolerated dose, and assess preliminary efficacy of the combination of ADG116 and pembrolizumab.

Additionally, the ongoing ADG116-1003 trial is on track to expand with two combination cohorts investigating safety and preliminary efficacy of ADG116 with either toripalimab or ADG106 in patients with advanced/metastatic solid tumors.

On November 29, 2021 Ablaze Pharmaceuticals ("Ablaze"), a clinical-stage pharmaceutical company focused on the development and commercialization of innovative targeted radiopharmaceutical therapies (TRT) against tumor targets, reported a $75 million Series A financing round (Press release, Ablaze Pharmaceuticals, NOV 29, 2021, View Source [SID1234596220]). The financing was co-led by Vivo Capital and AdvanTech Capital with participation from RAYZ Investments, Nan Fung Life Sciences, Pivotal bioVenture Partners China, venBio Partners, Samsara BioCapital and Venrock Healthcare Capital Partners.

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"Targeted radiopharmaceutical therapies represent the next foundational modality to treat cancer," said Dr. Ken Song, co-founder and Chairman of the Board of Ablaze and President and CEO of RayzeBio, Inc. "In forming Ablaze, we realized to be successful, it was critical to have a company focused on the China market and focused on radiopharmaceuticals."

With TRT gaining broader interest and adoption, Ablaze was formed to become the leading radiopharmaceutical company to introduce TRT products to the Greater China market. Led by an experienced team and a strong investor syndicate, Ablaze started on a solid footing, anchoring with a strategic RayzeBio in-licensing agreement, and a partnership with an academic institution on a clinical stage asset. Upon closure of the Series A, Ablaze is also actively exploring other potential partnerships, and building strong internal development capabilities.

"TRT is an emerging field that has already demonstrated tremendous clinical efficacy in treating cancer worldwide. We are privileged to have an opportunity to partner with Ablaze and the RayzeBio team in developing this category of potentially life-saving therapeutics for cancer patients in China." said Dr. Hongbo Lu, Managing Partner of Vivo Capital.

Proceeds from the Series A financing will be used by Ablaze to establish a leading pipeline of advanced TRT products for the treatment of solid tumors, expand the leadership team, build up infrastructure for radiopharmaceuticals and secure further strategic collaborations. The board of directors include Dr. Alex Qiao, co-founder and President and CEO of Ablaze Pharmaceuticals, Dr. Hongbo Lu, Benjamin Qiu, Partner at AdvanTech Capital, Dr. Aaron Royston, Managing Partner at venBio Partners, and Dr. Ken Song as well as Norman Tse, Vice President at Nan Fung Life Sciences as board observer.

"We believe Ablaze is bringing world class design of TRT products as well as clinical expertise to China through collaborations with global leaders in TRT, and is determined to be a leading player in China’s TRT innovations" said Mr. Benjamin Qiu.

"We are excited about this opportunity to bring a novel class of therapeutic products to benefit patients in China," said Dr. Alex Qiao. "This investment from top tier investors in China and abroad provides a strong endorsement to Ablaze’s vision and business model. We look forward to creating the best and differentiated medicines to address unmet medical needs in China."

On November 29, 2021 Kheiron Medical Technologies reported its new collaboration with researchers at Stanford University to design functional proof-of-concept deep learning models to solve clinical problems in novel ways, starting with Non-Hodgkin’s Lymphoma (NHL) (Press release, Stanford University, NOV 29, 2021, View Source [SID1234596219]). With the collaboration, Kheiron, which has pioneered the development and deployment of artificial intelligence solutions to help radiologists detect breast cancer earlier, will leverage its existing technologies and expertise to expand into new imaging modalities and cancer types. This furthers its mission of transforming cancer diagnostics through the power of deep learning.

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The collaboration aims to harness the collective expertise of the Stanford Center for Artificial Intelligence in Medicine & Imaging (AIMI Center) and Kheiron. This endeavour will be referred to as ‘The Kaplan Project’ in honor of Stanford’s former radiation oncology leader, Dr. Henry Kaplan, who in the 1960s developed some of the earliest treatments for lymphoma. The Kaplan Project aligns to the AIMI center’s mission, where interdisciplinary expertise is the foundation to help solve clinically important problems in medicine using AI.

"Projects like this one are so exciting because they capitalize on collaborations not only between clinicians and data scientists, but also between academics and industry," said Dr. Curt Langlotz, Director of the AIMI Center.

The purpose of staging lymphoma is to quantify the extent of disease, guide decisions around therapy, and provide a baseline prior to treatment. For oncological radiologists, the tasks of staging and evaluating post-treatment response on PET/CT scan images is manual and time-consuming.

The Kaplan Project will seek to apply Kheiron’s deep learning technology to FDG-PET/CT images of lymphoma patients to enhance two key radiologist outcomes: improving radiologist efficiency and improving radiologist accuracy.

"This groundbreaking project marks a new chapter in the application of AI to transform cancer diagnostics across the entire patient pathway," said Dr. Peter Kecskemethy, CEO of Kheiron. "Uniting new deep learning technologies with the clinical expertise of academic research institutions like Stanford will lead to the development of a completely new category of AI diagnostics and ultimately improve patient outcomes."

"Our project aims to improve a time-consuming and mostly qualitative process, the longitudinal assessment of whole-body FDG-PET/CT scans, using deep learning to augment imaging specialists," said Dr. Guido A. Davidzon, Clinical Associate Professor at Stanford University. "The overarching goal is to reduce the time needed to evaluate a PET scan, and by improving our throughput, ultimately increase patient access to a well-established noninvasive diagnostic imaging tool used by oncologists in the care of cancer."

On November 29, 2021 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the filing of a clinical trial for HLX301, a Recombinant Humanized Anti-PDL1 and Anti-TIGIT Bispecific Antibody, in Patients with locally advanced or metastatic solid tumours has been approved by the Bellberry Human Research Ethics Committee ("HREC"), and Clinical Trial Notification ("CTN") has been acknowledged by the Therapeutic Goods Administration ("TGA"), Australia (Press release, Shanghai Henlius Biotech, NOV 29, 2021, View Source [SID1234596218]). The Phase 1 clinical study in Australia is intended to be initiated soon. No bispecific antibody targeting PD-1/PD-L1 and TIGIT has been approved for marketing globally yet.

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Immunotherapies targeting immune checkpoint protein interactions between ligands and receptors offer a novel way to attack tumour cells in recent years. PD-1/PD-L1 plays a vital role in immune suppression; PD-1 and PD-L1 inhibitors show significant effectiveness in cancer treatment. TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains) is an inhibitory receptor, mainly expressed on natural killer (NK) cells and activated T cells and T regulatory cells. TIGIT binds to the major ligand CD155 (poliovirus receptor, PVR), mainly expressed on antigen-presenting cells (APC) or tumour cells, to down-regulate T cell and NK cell functions. TIGIT can inhibit innate and adaptive responses in various mechanisms and act as a "brake" like PD-1/PD-L1 does to stop T cells from attacking tumours. Several pre-clinical studies have indicated that TIGIT blockade may be effective against multiple advanced cancers, including NSCLC, GC, melanoma, and MM.

Independently developed by Henlius, HLX301 is an innovative anti-PD-L1 and anti-TIGIT bispecific antibody. Its TIGIT binding domain is derived from VHH fragments with high affinity and specificity to TIGIT, selected from the company’s synthetic humanized llama VHH library. Pre-clinical studies reported that HLX301 can simultaneously block both PD-1/PDL1 and TIGIT/PVR pathways, restore TCR signaling, inhibit tumour growth, and has good tolerance and safety. These results suggested that HLX301 is superior to blocking either pathway alone or anti-PD-L1 + anti-TIGIT combination therapy, paving the way for further clinical development.

Underpinned by the patient-centric strategy, Henlius achieves an overall layout of the immune checkpoint products of PD-1/L1, CTLA-4, LAG-3, BRAF, etc., proactively exploring immuno-oncology combination therapy, bispecific antibodies and ADC. Looking forward, Henlius will continue strengthening the in-licensing and collaboration on external innovative assets and bringing high-quality and affordable therapies to patients worldwide.