On October 22, 2021 Theratechnologies Inc. (Theratechnologies, or Company) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the publication of a peer-reviewed article demonstrating that the Company’s novel investigational peptide-drug conjugates (PDCs) TH1902 and TH1904, derived from its SORT1+ Technology, are effective in inhibiting vasculogenic mimicry (VM) in in vitro ovarian and triple negative breast cancer (TNBC) models (Press release, Theratechnologies, OCT 22, 2021, View Source [SID1234596236]).

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The article was published in the science journal Frontiers in Oncology and is titled "New Peptide-Drug Conjugates for Precise Targeting of SORT1-Mediated Vasculogenic Mimicry in the Tumor Microenvironment of TNBC-Derived MDA-MB-231 Breast and Ovarian ES-2 Clear Cell Carcinoma Cells."

"The results published in Frontiers in Oncology showcase for the first time that the sortilin receptor plays a role in the formation of VM, which is associated with cancer progression and resistance. By targeting SORT1, TH1902 and TH1904 have the potential to inhibit VM and cancer cell growth," said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer at Theratechnologies. "This recognition by our scientific peers highlights the great potential of our PDCs as a unique and effective vehicle for the potential treatment of many types of cancers in which SORT1 receptors are overexpressed and provides additional evidence that SORT1 plays a major role in the generation of VM, particularly in TNBC and ovarian cancer."

The article is the first to report that SORT1 plays a key role in VM formation and highlights the novel results from preclinical models evaluating the efficient inhibitory properties of TH1902 and TH1904 against VM in in vitro ovarian and TNBC cell models. These results further support the expectation that TH1902 and TH1904 may alter the VM process by bringing anticancer drugs, like docetaxel and doxorubicin, into SORT1-positive cancer cells.

The article can be accessed online here.

About Vasculogenic Mimicry
The formation of microvascular channels by deregulated cancer cells leads to aggressive, metastatic and resistant cancer cells and is known as vasculogenic mimicry. VM is believed to be associated with tumor growth, resistance and poor prognosis in many types of aggressive cancers including ovarian and TNBC.

About SORT1+ Technology
Theratechnologies is currently developing a platform of new proprietary peptides for cancer drug development targeting SORT1 receptors called SORT1+ TechnologyTM. SORT1 is a receptor that plays a significant role in protein internalization, sorting and trafficking. It is highly expressed in cancer cells compared to healthy tissue making it an attractive target for cancer drug development. Expression has been demonstrated in, but not limited to, ovarian, triple-negative breast, endometrial, skin, lung, colorectal and pancreatic cancers. Expression of SORT1 is associated with aggressive disease, poor prognosis and decreased survival. It is estimated that the SORT1 receptor is expressed in 40% to 90% of cases of endometrial, ovarian, colorectal, triple-negative breast and pancreatic cancers.

The Company’s innovative peptide-drug conjugates (PDCs) generated through its SORT1+ TechnologyTM demonstrate distinct pharmacodynamic and pharmacokinetic properties that differentiate them from traditional chemotherapy. In contrast to traditional chemotherapy, Theratechnologies’ proprietary PDCs are designed to enable selective delivery of certain anticancer drugs within the tumor microenvironment, and more importantly, directly inside SORT1 cancer cells. Commercially available anticancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies’ PDC to specifically target SORT1 receptors. This could potentially improve the efficacy and safety of those agents.

In preclinical data, the Company’s SORT1+ TechnologyTM has shown to improve anti-tumor activity and reduce neutropenia and systemic toxicity compared to traditional chemotherapy. Additionally, in preclinical models, SORT1+ TechnologyTM has shown to bypass the multidrug resistance protein 1 (MDR1; also known as P-glycoprotein) and inhibit the formation of vasculogenic mimicry – two key resistance mechanisms of chemotherapy treatment.

About TH1902
TH1902 combines Theratechnologies’ proprietary peptide to the cytotoxic drug docetaxel. TH1902 is currently Theratechnologies’ lead investigational PDC candidate for the treatment of cancer derived from its SORT1+ Technology. The FDA granted fast track designation to TH1902 as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. TH1902 is currently being evaluated in a Phase 1 clinical trial for the treatment of cancers where the sortilin receptor is expressed.

The Company is also evaluating TH1904 in preclinical research, a second PDC derived from its SORT1+ TechnologyTM TH1904 is conjugated to the cytotoxic drug doxorubicin.

The Canadian Cancer Society and the Government of Quebec, through the Consortium Québécois sur la découverte du médicament (CQDM), contributes a total of 1.4 million

On October 22, 2021 Egle Therapeutics SAS (Egle), an emerging biotechnology company focused on developing First-In-Class immunotherapies targeting immune suppressor regulatory T-cells (Tregs) for oncology and autoimmune diseases, reported that it has completed a €40M ($46.4M) Series A financing (Press release, Egle Therapeutics, OCT 22, 2021, View Source [SID1234591777]). The Series A was co-led by LSP and Bpifrance through their InnoBio 2 fund. Fund+, Bioqube Ventures and Takeda Ventures, Inc. also participated in this round.

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Egle Therapeutics was founded in early 2020 with a vision to become a game changer in the field of Tregs immunomodulation through the unique concept of Tregs starving and specifically targeting the most immunosuppressive ones. Spun out of Institut Curie, Egle’s scientific foundation leverages unprecedented, computational-based, IL-2 modified variants and newly tumor-associated Treg targets to build a furnished pipeline of First-In-Class immunocytokines against Tregs. The new capital will be used primarily to advance 2 leads assets into the clinic and further strengthen its internal drug pipeline.

"Closing a substantial Series A of €40M from a high-quality syndicate of renowned investors, as well as a partnership with a top big pharma like the one we have announced with Takeda in June 2020, all in less than 18 months, puts Egle on a trajectory to execute its vision of tackling regulatory T cells to restore immunity in patients suffering from cancer and autoimmune diseases" commented Luc Boblet, co-founder and CEO of Egle. "The funding will give us appropriate resources to push the first Treg starvers into the clinic and we feel very privileged to undertake such responsibility for the benefit of the whole patient community".

The investor syndicate will join the Egle Therapeutics Board which will consist of Felice Verduyn-van Weegen (LSP), Vincent Brichard (LSP), Jean-Francois Morin (Bpifrance – InnoBio 2) and Sacha Mann (Takeda Ventures). Philippe Monteyne (Fund+), Jacques Mizrahi (Bioqube Ventures) and Elisa El Nouchi (Bpifrance InnoBio 2) will join as observers.

"Egle represents a strategic investment in a First-In-Class technology platform based on innovative research with novel T regulatory modulations and potential in the oncology and auto-immunity fields", commented Vincent Brichard, Venture Partner at LSP. "We feel privileged to be part of such an exciting company, with world class science and look forward to build it out together with the team" adds Felice Verduyn-van Weegen, partner at LSP.

"InnoBio 2 strives to invest in breakthrough ideas and to promote First-In-Class drugs candidates. We are delighted to have co-led a financing round that will enable Egle Therapeutics to broadly invest in its platform technologies, development programs, people and ultimately, towards delivering a pioneering new generation of immunotherapies to patients in need," said Jean-François Morin, Investment Director at Bpifrance.

On October 22, 2021 The Board of Directors of Alligator Bioscience AB (publ) ("Alligator" or "the Company") reported that it has previously, subject to approval by the Extraordinary General Meeting on 8 November 2021, resolved to carry out a rights issue of shares with preferential rights for the Company’s existing shareholders of approximately SEK 257 million (the "Rights Issue") (Press release, Alligator Bioscience, OCT 22, 2021, View Source [SID1234591762]). Through the press release issued on 7 October 2021 regarding the board’s decision to carry out the Rights Issue, Alligator announced that all members of the Company’s board and management with shareholdings in the Company had expressed their intention to subscribe for their respective pro rata share in the Rights Issue, in addition to the other subscription- and guarantee commitments already entered into, which secure the Rights Issue to 100 percent. Alligator hereby announces that all members of the Company’s board and management with shareholdings in the Company now have, via subscription commitments, formally undertaken to subscribe for their respective pro rata share in Rights Issue.

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Through the press release issued on 7 October 2021 regarding the board’s decision to carry out the Rights Issue, Alligator announced that the Company had received subscription commitments from a selection of the Company’s larger existing shareholders, including AP4, Roxette Photo NV and Omentum S.A. In the press release it was also announced that all members of the Company’s board and management with shareholdings in the Company had expressed their intention to subscribe for their respective pro rata share in the Rights Issue. Since the announcement, the Company has now received subscription commitments from all members of the Company’s board and management with shareholdings in the Company, including Søren Bregenholt (CEO), Anders Ekblom (Chairman of the board), Marie Svensson (CFO), Peter Ellmark (CSO), Veronica Wallin (board member) and Hans-Peter Ostler (board member), to subscribe for their respective pro rata share in the Rights Issue, amounting to a total of approximately SEK 0.7 million, which means that the Company has received subscription commitments amounting to a total of approximately SEK 44 million in connection to the Rights Issue, corresponding to approximately 17 percent of the Rights Issue. No compensation is paid for received subscriptions commitments.

For more information regarding the Rights Issue, see the Company’s press release issued on 7 October 2021 and the prospectus (the "Prospectus") that the Company is expected to publish around 9 November 2021.

Advisers

DNB Markets, a part of DNB Bank ASA, Sweden Branch and Redeye AB act as Joint Global Coordinators in connection with the Rights Issue. Setterwalls Advokatbyrå AB acts as legal adviser to Alligator and Baker & McKenzie Advokatbyrå KB acts as legal adviser to the Joint Global Coordinators in connection with the Rights Issue. Aktieinvest FK AB acts as the issuing agent in the Rights Issue.

On October 22, 2021 Invitae (NYSE: NVTA), University College London (UCL), and the Francis Crick Institute reported new data from their TRACERx lung cancer research collaboration funded by Cancer Research UK and sponsored by UCL (Press release, Invitae, OCT 22, 2021, View Source [SID1234591778]). The data, presented by Professor Charles Swanton of UCL and the Francis Crick Institute at the International Society of Liquid Biopsy (ISLB) Congress, further validate the value of liquid biopsy as a less invasive and more comprehensive approach to guiding personalized cancer treatment in the absence of detectable disease by clinical imaging. Previously reported findings from the TRACERx cohort found that monitoring for cancer circulating tumor DNA (ctDNA) based minimal residual disease (MRD) detected relapse of non-small cell lung cancer (NSCLC) up to three years earlier than standard of care imaging surveillance in some instances.1

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

The study used a new blood-based informatic tool called ECLIPSE (Extraction of CLonality from LIquid bioPSiEs) with an earlier iteration of the Invitae Personalized Cancer Monitoring (PCM) liquid biopsy assay to analyze plasma samples of patients in the TRACERx study. With this approach, data demonstrated multiplex-anchored PCR sequencing of the plasma samples enhanced MRD lead times relative to standard of care surveillance scanning and allowed holistic sampling of clonal dynamics, or tumor heterogeneity, with prognostic implications for disease progression.

"Tumours are highly heterogeneous and standard biopsies can miss important tumor traits. Our findings from applying our novel ECLIPSE software with Invitae’s multiplex-anchored PCR technology, which powers the Invitae PCM assay, are promising. They underscore the tremendous potential of PCM for providing representative tumor sampling throughout the disease course, and most importantly at an early stage or at early recurrence in the absence of disease on standard imaging, which may in the future inform clinical trial stratification and the best treatment plans for patients," said Professor Charles Swanton, Cancer Research UK’s Chief Clinician and a 2021 ISLB award recipient for outstanding scientific contribution in liquid biopsy. "Better understanding the true pathology of a patient’s tumor, including driver and passenger clonal mutations, and identifying MRD earlier, are key to unlocking personalized cancer care and changing the paradigm of cancer drug development towards earlier intervention in the adjuvant setting where cures are more readily achievable."

Invitae’s PCM is a pan-cancer, tumor-informed liquid biopsy assay that uses next-generation sequencing powered by Anchored Multiplex PCR (AMP) to monitor MRD with high sensitivity at low variant allele fractions. The service employs a combination of a tumor profile, blood tests and personalized assays based on a patient’s tumor with the goal of earlier detection of cancer recurrence through ctDNA before it is detectable by imaging or other conventional methods. ECLIPSE, developed by the Cancer Research UK TRACERx team at UCL and the Francis Crick Institute, uses a standardized algorithm that helps resolve tumor tissue-based sample bias. Coupling Invitae’s PCM assay with ECLIPSE, the researchers analyzed 972 longitudinal plasma samples from 136 TNM I-III NSCLC patients in TRACERx who had undergone multiregion whole exome sequencing of primary tumor and relapse tissue and had 364 surveillance scans. Seventy-five of these patients experienced a recurrence of their surgically resected disease.

The researchers concluded that multiplex-anchored PCR with trinucleotide specific background models improves NSCLC relapse detection compared to standard of care clinical follow up. Using ECLIPSE, plasma samples of less than 1% purity can be used to accurately profile the clonal structure of tumors at diagnosis, during treatment and at relapse, which impacts patient outcome and has the potential to guide personalized medicine.

"Determining the best treatment plan for a cancer patient depends on several factors, including the results of current disease monitoring. Unfortunately, traditional monitoring methods such as imaging and tissue biopsy are insensitive when it comes to adequately representing a tumor or detecting relapse early in a patient’s treatment cycle," said Robert Nussbaum, M.D., chief medical officer of Invitae. "These findings further validate the role of PCM in determining a therapy’s effectiveness and identifying relapses more quickly, both of which are essential to optimizing personalized treatment plans."

PCM and other liquid biopsy approaches for monitoring MRD have the potential to become a mainstay in personalized oncology. PCM could be applied in a variety of ways to help improve patient care and prolong survival outcomes, including monitoring for recurrence, monitoring a patient’s response to therapy to inform treatment decisions, and improving clinical trial designs to help get new therapies to market sooner.

About TRACERx Study

TRACERx (Tracking Cancer Evolution through therapy (Rx)) lung study is the single biggest investment in lung cancer research by Cancer Research UK. Taking place over nine years, we believe the translational research programme is the first study to look at the evolution of cancer in real time and immense detail. Researchers follow patients with lung cancer all the way from diagnosis through to either disease relapse or cure after surgery, tracking and analysing how their cancer develops. TRACERx is led by UCL (University College London) via the Cancer Research UK Lung Cancer Centre of Excellence and also supported by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre, Francis Crick Institute and the Rosetrees Trust.

On October 22, 2021 Chimeric Therapeutics (ASX:CHM, "Chimeric"), a clinical-stage cell therapy company and the ASX leader in cell therapy, reported the successful completion of manufacturing for CHM 2101 research grade plasmids, a critical first step in the development of CDH17 CAR T (Press release, Chimeric Therapeutics, OCT 22, 2021, View Source [SID1234591763]).

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Manufacturing of CAR T therapies is dependent upon plasmids and viral vectors that hold the genetic instructions for each specific CAR T product. Plasmids are small DNA molecules that carry genetic instructions and their successful manufacture marks an important early step for all CAR T therapies.

In collaboration with the University of Pennsylvania, all of the research grade helper and transfer plasmids for the CDH17 CAR T have been completed and released. The achievement of this first step in CAR T manufacturing enables progression to research vector manufacturing, GMP plasmid and vector manufacturing and advancement of technical operations in readiness for the CDH17 CAR T phase 1 clinical trial.

Chimeric’s CEO and Managing Director Jennifer Chow said: "We are very pleased that we have been able to achieve this key first step so rapidly after licensing. This accomplishment speaks to the commitment and drive that the Chimeric and University of Pennsylvania teams share to move this important CAR T forward to Phase 1 clinical trials."

In addition to commencing the CDH17 CAR T Phase 1 trial in 2022, Chimeric is also progressing its CLTX CAR T Phase 1 clinical trial in glioblastoma (brain cancer) at The City of Hope Cancer Centre in California, where patients are now receiving second dose levels.

Authorised on behalf of the Chimeric Therapeutics board of directors by Chairman Paul Hopper