On November 30, 2021 NeoTX Therapeutics (NeoTX), a clinical-stage immuno-oncology company, reported that the preclinical data on naptumomab estafenatox (NAP) enhancing the potency of CAR-T cells was presented on Nov 12th at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting at the Walter E. Washington Convention Center, Washington D.C. (Press release, NeoTX, NOV 30, 2021, View Source [SID1234640356]).

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Clinical CAR-T therapy currently has limited efficacy against solid tumors due to low trafficking to the tumor, limited cell expansion in patients, tumor antigen heterogeneity, and an immunosuppressive microenvironment. NeoTX presented data that shows that NAP generates more potent CAR-T cells and acts synergistically against tumor cell lines in vitro. NAP is a fusion protein that consists of genetically engineered Superantigens (Sag) linked to Fragment antigen-binding (Fab) moieties directed to tumor-associated antigens, turns "cold tumors hot" and, in preclinical models, can lead to long-term memory responses.

The ability of NAP administration to activate T cells outside of the immunosuppressive microenvironment, promote T cell infiltration into the tumor and induce long-term memory responses strongly suggests that the combination of CAR-T cells with NAP may overcome the limited effect of CAR-T therapy against solid tumors. To access the presented poster, please click here.

On November 30, 2021 Neuramedy reported that NM-101 (tomaralimab), a monoclonal antibody against TLR-2 Alpha-synucleinopathies are neurodegenerative diseases caused by the abnormal accumulation of misfolded alpha-synuclein in neurons and glial cells (Press release, Neuramedy, NOV 30, 2021, View Source [SID1234632172]). There are three major types of alpha-synucleinopathies: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

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Misfolded alpha-synucleins can promote neuroinflammation and neuronal loss and also spread to the neighboring neurons, which are mediated by Toll-like Receptor-2 (TLR-2). Furthermore, TLR-2 is found to be up-regulated in alpha-synucleinopathies.

Therefore, the inhibition of TLR-2 would be one of the promising therapeutic strategies to slow down or halt the progression of alpha-synucleinopathies, along with the therapies targeting alpha-synuclein.

Neuramedy, headquartered in Seoul, is a biotech company focusing on novel therapeutic approaches to treat alpha-synucleinopathies, based on the findings above.

Neuramedy’s NM-101 (tomaralimab) is a first-in-class humanized IgG4 monoclonal antibody against TLR-2 which was originally developed and termed ‘OPN-305’ by Opsona Therapeutics (Dublin, Ireland) for the treatment of myelodysplastic syndrome in 2015. Neuramedy took over the patent and global rights for tomaralimab from Opsona in 2019 and is now applying it to PD.

The company is expanding the potential application of tomaralimab to the treatment of Alzheimer’s disease (AD) in conjunction with Amyloid Solution (Seongnam, South Korea) under the name of ‘AS-M801’, considering that TLR-2 is also up-regulated in beta-amyloidopathy like AD and activated by beta-amyloid as in PD and by alpha-synuclein.

Neuramedy is also developing its novel BBB-penetrating antibody (NM-301) for the treatment of neurodegenerative diseases, in collaboration with Aptamer Sciences, a front-runner in Aptamer Technology that will provide antibodies with a BBB shuttle.

In parallel with these, the company is additionally developing its innovative small molecules (NM-401, NM-402, and NM-403) that can inhibit the aggregation of alpha-synucleins for the treatment of various alpha-synucleinopathies (PD, MSA, and DLB), conjointly with Yungjin Pharm.

Neuramedy is planning to initiate its phase 1b/2a clinical trials of NM-101 for the treatment of AD in the U.S. next year.

On November 30th 2021 Defence Therapeutics, is a publicly-traded biotechnology company working on engineering the next generation vaccines, Antibody Drug Conjugates, ADC products, and cancer therapeutics using its proprietary AccumTM platform (Press release, Defence Therapeutics, NOV 30, 2021, View Source [SID1234626241]). The core of Defence Therapeutics platform is its AccumTM technology, which enables precision delivery of proteins of pharmacological interest to target cells and increases the intracellular accumulation to these targeted cells. As a result, increased efficacy and potency can be reached against catastrophic illness such as cancer and infectious diseases. With four new patents filed over the last year, Defence is providing increased company IP with its technologies. Defence’s research activities conducted over the last year along with future clinical plans to prove validation is ongoing.

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Development of the core Technology
The Company’s core technological research is based around addressing a major and common challenge in both the vaccine and antibody drug conjugates ("ADCs") fields limiting their efficacy. When the target cell binds and internalizes an antigen or an ADC, the complex is entrapped inside intracellular small vesicles named endosomes. Ultimately, these endosomes undergo maturation consequently leading to their degradation prior to eliciting their respective role/function. The Company’s goal is to use the AccumTM enhancer formulation to improve intracellular delivery of biological therapeutic agents by inducing their escape to the cytosol consequently improving their therapeutic efficacy.

Effective Cellular Vaccine Design
The AccumTM technology is highly suitable to the vaccination field. More specifically, antigens that are normally captured by dendritic cells ("DCs") – the best antigen-presenting cells present in our body- are first entrapped in endosomes. While maturation of these endosomal organelles occurs, the pH decreases (becomes acidic ⁓4-5) in order to trigger the activation of specific enzymes as a means to initiate non-specific antigen degradation. As a result, the generated fragments can then pass-through endosomal pores to reach the cytoplasm where specific antigen degradation takes place by the proteasomal machinery. Although this process occurs naturally, the generated antigen fragments are often damaged, which renders them unsuitable for optimal immune stimulation. By using the AccumTM technology, captured antigens are preserved in their natural conformation while being delivered to the cytoplasm. As such, proteasomal degradation ends-up leading to a higher number of immunogenic and stable peptides presented at the surface of DCs and capable of eliciting potent T-cell activation.

Research conducted by the Company has found that the addition of Accum-linked antigens to allogeneic DCs (AccuVAC-D001) enhances the therapeutic efficacy of the vaccine leading to a survival rate of 70-80% in contrast to 0-20% obtained with current experimental DC-based vaccines. With the completion of such study, Defence has signed an agreement with a Canadianbased clean room to initiate dry runs of its DC vaccine. The objective is to complete all needed GLP studies by Q1 2022 and initiate a Phase I trial against melanoma in the UK by mid 2022.

The development of protein-based vaccines for infectious diseases (COVID and HPV)
In parallel, the Company has already completed all pre-clinical work related to its COVID-19 vaccines. The first vaccine (DTC-PT001) is an injectable formulation delivered with an FDAapproved adjuvant. Generated data demonstrated potent and sustainable production of IgG titers (over 16 weeks), which was also highly reactive against all tested variants. In addition, the immunogenicity of the vaccine was highly comparable between rodent (mice) and non-rodent (rabbit) models. Furthermore, vaccination of hamsters (third model-GLP study) followed by viral challenge showed potent protection with no noted side effects.

The second vaccine formulation (DTC-IN003) is a transmission-blocking vaccine designed to halt infection as opposed to lowering the pathophysiology of the virus. In this case, the vaccine is delivered intranasally with a special adjuvant (designed for intranasal vaccination). This vaccine not only triggered the production of IgAs at mucosal sites (entry site of the virus), but systemic immunity was also observed and generated antibodies cross-reacted with all tested variants. A GLP challenge study is currently ongoing with final data to be obtained by the end of December 2021.

Another infectious disease vaccine in development at Defence Therapeutics is AccuVAC-PT009 targeting HPV. This vaccine is using a mixture of L1 proteins (derived from different HPV strains) linked to AccumTM and tested for their ability to confer protective antibodies against the HPV virus. The potency of the AccuVAC-PT009 vaccine will be compared to the commercially available Gardasil-9 vaccine in terms of its immunogenicity (prophylactic vaccine). In addition, Defence is working on a second HPV-related vaccine but targeting cervical cancer (AccuVACPT0067). The objective of this vaccine is to modify both E6 and E7 proteins to covalently link AccumTM then test the vaccine for its ability to treat pre-established cervical cancer. Results of the pre-clinical studies will be available by early 2022.

Effective Design of ADCs
One challenge posed by ADCs is insufficient intracellular accumulation of the delivered chemotherapeutic necessary for potent tumor killing. Defence has demonstrated that the AccumTM technology enhances the ability of ADC Kadcyla (T-DM1) to specifically kill breast cancer cells. AccumTM improved the escape of ADC Kadcyla from endosomes while targeting the nucleus. Defence believes that the AccumTM technology will be able to increase T-DM1 effectiveness enabling the treatment to overcome resistance mechanisms such as reducing the number of cell surface receptors, therefore limiting the potency and delivery of T-DM1 inside the cell. The Company has formed a strategic collaboration with two European institutions to further develop its Accum-ADCs platform.

The AccuTOX Program
The AccumTM technology platform is very efficient at enhancing intracellular delivery of proteins of pharmacological interests such as vaccine antigens or ADCs. However, a novel anti-cancer function was recently discovered for "free" AccumTM. More specifically, when directly delivered without direct linking onto protein, the AccumTM moiety behaves as a toxic "silver bullet" to cancer cells. So far, the Defence team has engineered and tested a large library of AccumTM variants and identified a lead molecule capable of killing breast, colon, melanoma and lymphoma cancers. A GLP study is currently ongoing with final results expected by the end of 2021 with plan to initiate a Phase I trial against breast cancer in Q2 of 2022.

On November 30, 2021 Jazz Pharmaceuticals plc (NASDAQ: JAZZ) along with partner PharmaMar (MSE: PHM) reported the commercial availability of ZepzelcaTM (lurbinectedin) after receiving conditional approval by Health Canada in September 2021 (Press release, Jazz Pharmaceuticals, NOV 30, 2021, View Source,Health%20Canada%20in%20September%202021%20 [SID1234597678]). Zepzelca is the first new treatment in Canada for adult patients with Stage III or metastatic small cell lung cancer (SCLC) who have progressed on or after platinum-containing therapy in more than a decade.1

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Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in Canada.2 SCLC is the most aggressive form of lung cancer.3 It represents a significant health burden, with more than 4,000 cases annually across Canada, and accounts for about 13 per cent of all lung cancers. While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that may not respond to treatment.4 The general five-year survival rate for people with SCLC is 7 per cent.5

"This is a significant milestone for people with relapsed small cell lung cancer and further demonstrates Jazz’s commitment to developing life-saving medicines for people with limited options." says Paul Petrelli, general manager, Jazz Pharmaceuticals Canada Inc. "We are proud to introduce this meaningful new treatment to patients in Canada."

The Health Canada conditional approval of Zepzelca was based on overall response rate and duration of response.1 The planned confirmatory study will be initiated later this year.

"Small cell lung cancer is a disease with a particularly poor prognosis. While chemotherapy is highly effective for most patients initially, the vast majority progress within months of completing treatment. Once the cancer starts to regrow, we are very limited in what we can do to manage their condition," says Dr. Rosalyn Juergens from McMaster University, Juravinski Cancer Centre. "Further research is needed in Canada but the addition of Zepzelca to the second line therapy landscape is welcome news for doctors, patients and their families."

"Patients with small cell lung cancer in the second line and their families have been on the sidelines for far too long. The availability of Zepzelca in Canada is a great new option," says Shem Singh, executive director, Lung Cancer Canada. "It gives patients and their families hope – hope for more time, hope for one more family celebration, hope for one more hug – and that’s a very powerful thing. With time being of the essence for small cell lung cancer patients, we call on stakeholders to quickly make this treatment publicly funded for those who can’t wait."

The conditional approval of Zepzelca by Health Canada is based on results from a Phase II open-label, multi-centre, multi-cohort, single-arm study (Study B-005) consisting of 105 SCLC patients who were treated with 3.2 mg/m2 Zepzelca, administered as a 60-minute intravenous infusion repeated every 21 days (one-cycle).1 The data showed that in patients with relapsed SCLC, Zepzelca demonstrated an overall response rate of 35 per cent and a median duration of response of 5.3 months as measured by investigator assessment.1

About Zepzelca(lurbinectedin)
Zepzelca is indicated for the treatment of adult patients with Stage III or metastatic SCLC who have progressed on or after platinum-containing therapy.1 Zepzelca works by preventing the cancer cells from growing and spreading to other parts in the body. Zepzelca also reduces the ability of other cells to support the growth of the cancer cells. This helps stop the growth of the cancer cells. The recommended Zepzelca dosing is 3.2 mg/m2 by intravenous infusion over 60 minutes repeated every 21 days until disease progression or unacceptable toxicity.

The most common (≥20%) reported adverse events (all grades) were fatigue (77%), nausea (37%), neutropenia (33%), decreased appetite (33%), musculoskeletal pain (31%), dyspnea (31%), constipation (31%), respiratory tract infection (26%), vomiting (22%), diarrhea (20%) and cough (20%).1

For more information, please refer to the product monograph for Zepzelca in Canada located here.

About SCLC
Small cell lung cancer is a fast-growing lung cancer that develops in the tissues of the lungs.6 By the time a person receives a diagnosis, it has typically spread (metastasized) outside of the lungs. This cancer is also more likely than other types of lung cancer to come back after treatment. Small cell lung cancer is sometimes, but not often, called oat cell cancer because the small, oval-shaped cells look like oat grains under a microscope. People with and without a smoking history are all at risk for lung cancer. However, small cell lung cancer almost always develops in people who have a long history of tobacco use.

On November 30, 2021 Synaffix B.V., a biotechnology company focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported the expansion of its license agreement with Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need (Press release, Synaffix, NOV 30, 2021, View Source [SID1234596604]).

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Under the expanded license agreement, Mersana will expand its access to Synaffix’s GlycoConnect site-specific ADC bioconjugation technology for six additional ADC targets. The license rights granted to Mersana are tied to specific ADC targets to be selected and provide non-exclusive access to deploy GlycoConnect site-specific ADC bioconjugation technology against the specified targets. Under the expanded deal, Synaffix is eligible to receive upfront and milestone payments on a per-target basis with a total potential deal value exceeding $1 billion plus royalties. This builds on the long-term relationship between the two companies announced in 2019.

Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics, said:

"Our collaboration with Synaffix and use of the GlycoConnect site-specific ADC bioconjugation technology has yielded highly innovative ADC products with superior characteristics. Based on the data that we generated to date across multiple programs, we have gained the confidence to significantly expand our collaboration with Synaffix and elect GlycoConnect as our preferred site-specific ADC bioconjugation technology."

Peter van de Sande, Chief Executive Officer of Synaffix, said:

"We are delighted to expand our collaboration with Mersana, a leader in ADC innovation, who will be utilizing our GlycoConnect platform to build out their pipeline with innovative ADC cancer therapeutics. We are honored to see the confidence that Mersana has placed in our platform, demonstrating once again the added value GlycoConnect can bring to innovative ADCs."

Mersana will continue to be responsible for the research, development, manufacturing and commercialization of any resulting ADC products.

This licensing agreement expansion follows three recent ADC technology out-licensing agreements with Kyowa Kirin, a global specialty pharmaceutical company; ProfoundBio, an emerging oncology biotherapeutics company; and Innovent Biologics, a leading biopharmaceutical company developing innovative medicines for the treatment of major diseases. Other collaborators include ADC Therapeutics and Shanghai Miracogen. Twelve ADCs using Synaffix’s technology are currently in development of which three are in clinical development.