On June 18, 2024 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecules and their formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, reported that in preclinical research, it’s lead drug formulation, Rutherrin, has demonstrated an ability to increase the efficacy of immunotherapy (Press release, Theralase, JUN 18, 2024, View Source [SID1234644440]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Immunotherapy, the latest technology in the war on cancer, can come in various forms; including: checkpoint inhibitors, Chimeric Antigen Receptor ("CAR") T-Cell therapy, cytokines, immunomodulators, cancer vaccines, monoclonal antibodies and oncolytic viruses, but the fundamental Mechanism Of Action ("MOA") of all of these immunogenic drugs is to stimulate the immune system to destroy cancer cells.

Cancer cells hide from the immune system by overexpressing proteins on their cellular surface, known as checkpoint proteins, that prevent the immune system from recognizing and subsequently destroying them. They thus remain incognito to the one failsafe that can protect the human body, the immune system.

The MOA of checkpoint inhibitors is to block the PD-L1 (checkpoint protein) on the cancer cell surface, allowing the immune system to detect and destroy the cancer cell; however, resistance to immunotherapy remains one of the major challenges in this form of treatment. In an attempt to overcome this resistance, multiple immunotherapy treatments are delivered to the patient, which may ultimately lead to a diminishing return in efficacy and a corresponding increase in patient serious adverse events and even treatment-related death.

Theralase’s latest research demonstrates that Rutherrin enhances the MOA of immunotherapy by not only killing cancer cells directly, but also significantly reducing the amount of PD-L1 proteins expressed by cancer cells; hence, reducing the number of target checkpoint proteins that need to be blocked by checkpoint inhibitors.

This results in an elegant one-two-three punch on the destruction of cancer cells; where, Rutherrin delivers the first punch, targeting and destroying cancer cells directly, as well as the second punch, by reducing the number of PD-L1 proteins expressed. This allows immunotherapeutic drugs to deliver the third and final punch, blocking the PD-L1 proteins remaining, allowing the immune system to significantly increase their recognition of cancer cells and hence their destruction. As a result, this technological advance increases both the safety and efficacy of immunotherapy, as less treatments would be required to induce the same clinical effect.

As a primary MOA, Rutherrin, has been demonstrated clinically to destroy NMIBC, when activated by light, and preclinically to destroy GBM and Non-Small Cell Lung Cancer ("NSCLC"), when activated by x-ray radiation.

As a secondary MOA, Rutherrin, has been demonstrated preclinically to unmask cancer cells through dual immunogenic check points; specifically, CD47 (previously reported by Theralase) and now PD-L1 inhibition. This down regulation of immunogenic check points allows the cancer cell to be detected and destroyed by the immune system, resulting in a process known as Immunogenic Cell Death ("ICD"). ICD is characterized by the secretion of Damage-Associated Molecular Patterns ("DAMPs"), which are transported to the cell surface during ICD.

Calreticulin ("CRT"), one of the DAMPs found in the lumen of the endoplasmic reticulum, is translocated to the surface of dying cells, after the induction of ICD, where it functions as an "eat me" signal for the immune system.

Dr. Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer of Theralase stated, "It is one of humanity’s greatest health challenges in the 21st century, that cancer of various forms, affects and kills millions of people each and every year, without discrimination. Immunotherapy is the latest technology that attempts to harness the power of the immune system to detect and destroy cancer cells; however, these same cancer cells, treated with immunotherapy, develop mechanisms to avoid detection by the immune system, which consequently has an adverse effect on how effectively they react to therapy. In that regard, in a clinical setting, the term "resistance to immunotherapy" is applied; primary resistance denoting a failure to respond to the treatment from day one, while secondary resistance denoting a relapse following the initial response to immunotherapy. Despite remarkable scientific progress in this field, attempts to develop new strategies against cancer resistance to immunotherapy have proven difficult. We are very pleased with the results of our latest research, demonstrating that our lead drug formulation, Rutherrin, is able to maintain a therapeutic balance between various "accelerators" and "brakes" of our immune system to ensure that it is sufficiently engaged in attack against malignant cells, while avoiding destruction of healthy cells and tissues."

Roger DuMoulin-White, B.E.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer of Theralase stated, "All cancer therapies, in their essence, attempt to destroy the disease, with minimal to no side effects and allow the patient a complete response with no recurrence; however, despite recent advances in the treatment of specific cancer types, many patients still struggle to respond to cancer treatments and are left with significant side effects. The PD-L1 (immune checkpoint protein) functions as a "brake" on the innate immune system, while Calreticulin ("eat me" signal) functions as an accelerator. We are very pleased to demonstrate that Rutherrin has the potential of releasing the "brake" and applying the "accelerator" to the immune system at the right time and thereby unleashing the power of our immune system to attack and destroy cancerous cells, while sparing healthy ones. By stimulating the inherent ability of our immune system to protect and defend our bodies against cancer, Rutherrin has the potential to establish an entirely new paradigm for cancer therapy."

On June 18, 2024 Precision-Panc team at the University of Glasgow, with their Co-Sponsor, NHS Greater Glasgow & Clyde, reported the opening of the Phase II PRIMUS-006 study evaluating IMM-101, a broad-spectrum immunomodulatory agent containing heat-killed, whole cell Mycobacterium obuense, in combination with gemcitabine and pembrolizumab as first-line treatment in patients with metastatic pancreatic cancer (Press release, Immodulon Therapeutics, JUN 18, 2024, View Source [SID1234644423]). The PRIMUS-006 study is part of the Precision-Panc Platform master protocol program, which is Co-Sponsored by NHS Greater Glasgow & Clyde and the University of Glasgow and co-ordinated by the Glasgow Oncology Clinical Trials Unit. PRIMUS-006 is endorsed by Cancer Research UK (CRUK Reference: A31505).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study is funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A., through its investigator-initiated program with provision of study drug and financial support.The study is also funded by Immodulon Therapeutics Ltd through its investigator-initiated program with provision of study drug and financial support for the study.

"The opening of the Phase II PRIMUS-006 study is an important milestone in the pursuit to develop new treatment options to improve the overall outcomes in patients diagnosed with pancreatic cancer," said Professor David Chang, principal investigator and professor of surgical oncology & honorary consultant pancreatic surgeon, Wolfson Wohl Cancer Research Centre, University of Glasgow and Glasgow Royal Infirmary. "The selection of IMM-101 to comprise part of the triplet combination reflects its potential to enhance anti-tumour activity alongside gemcitabine and pembrolizumab in patients with first-line metastatic pancreatic cancer," said Professor Jeff Evans of the University of Glasgow and Honorary Consultant in Medical Oncology at the Beatson West of Scotland Cancer Centre, Glasgow.

Pancreatic ductal adenocarcinoma (PDAC) tends to be poorly immunogenic with diminished antigen presentation and a highly immunosuppressive tumour micro-environment that further impedes the functional activation of cytotoxic T lymphocytes. Based on the ability of gemcitabine to enhance the expression of antigen-presenting molecules, its use in combination with IMM-101, a broad-spectrum immunomodulator with potential to sensitize pancreatic cancers to immune checkpoint inhibition, and pembrolizumab, MSD’s anti-PD-1 therapy, this novel combination has the potential to enhance anti-tumour efficacy in patients with first-line pancreatic cancer.

"This is an exciting opportunity to be part of a high caliber pancreatic cancer research program and reflects the potential of IMM-101 to become a backbone therapy in immunologically cold tumours by enhancing the efficacy of existing anti-cancer treatment options, including chemotherapy and checkpoint inhibitors," said Josefine Roemmler-Zehrer, MD, Associate Professor, and Chief Medical Officer of Immodulon. "We look forward to working with the Co-Sponsors NHS Greater Glasgow & Clyde and University of Glasgow, MSD and other key collaborators to support this study and advance our efforts to bring IMM-101 closer to patients diagnosed with pancreatic cancer and other solid tumours."

The Phase II PRIMUS-006 study is a single-arm clinical study evaluating IMM-101, gemcitabine and pembrolizumab as first-line combination triplet therapy in patients diagnosed with metastatic pancreatic cancer who are deemed not sufficiently fit enough to tolerate treatment consisting of two or more cytotoxic agents. As the overall objective of the study is to enhance the anti-tumour activity of immunotherapy, the primary endpoint of the study is the objective response rate as defined by RECIST 1.1. Key secondary endpoints include safety and tolerability, evaluation of progression-free survival, disease control rate and overall survival. Up to 50 patients with metastatic pancreatic ductal adenocarcinoma will be treated in the study from approximately 15-20 hospital sites in the United Kingdom.

About Pancreatic Ductal Adenocarcinoma (PDAC)

PDAC is the third most common cause of cancer death in the developed world. Approximately 50% of patients present with metastatic disease and most of the patients who present with resectable or locally advanced inoperable disease ultimately develop metastatic disease.

Gemcitabine monotherapy has modest clinical benefit and a marginal survival advantage in patients with metastatic PDAC. Better response rates and survival can be achieved with the FOLFIRINOX regimen, and with the addition of nab-paclitaxel to gemcitabine.

Nevertheless, overall survival remains disappointing with these combination cytotoxic chemotherapy regimens.
Furthermore, many patients are not fit enough to tolerate these combination regimens, and these patients are invariably excluded from participation in clinical trials because of lower performance status. Consequently, these patients represent a significant unmet clinical need and are in urgent need of novel therapeutic approaches.

About IMM-101

IMM-101 is a systemic, broad-spectrum immunomodulator containing heat-killed, whole cell Mycobacterium obuense, capable of generating a broad systemic innate and adaptive type 1 immune response with potential to treat immunologically ‘cold’ cancers, like pancreatic cancer. In the Phase II IMAGE-1 Study of IMM-101 in combination with gemcitabine, clinical data indicate that IMM-101 is well-tolerated and effective and that it has the potential as a first-line treatment to prolong progression-free survival in patients with advanced pancreatic ductal adenocarcinoma (PDAC) when compared to gemcitabine alone. The study data also suggest a beneficial effect on survival in patients with metastatic PDAC. Immodulon is currently prioritizing the initiation of a Bayesian adaptive pivotal study for IMM-101 in PDAC that can be expanded to evaluate IMM-101 in other immunologically ‘cold’ tumours across multiple parallel arms.

On June 18, 2024 Zentalis Pharmaceuticals, a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on the following studies of azenosertib: the Phase 1 ZN-c3-001 dose-escalation study in solid tumors, the Phase 2 ZN-c3-005 (DENALI) study in platinum-resistant ovarian cancer (PROC) and the Phase 2 ZN-c3-004 (TETON) study in uterine serous carcinoma (USC) (Press release, Zentalis Pharmaceuticals, JUN 18, 2024, View Source [SID1234646059]). This action follows two recent deaths due to presumed sepsis in the DENALI study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Patient safety is our top priority and any deaths that occur in the setting of clinical trials are unfortunate. We are working closely with the FDA to resolve this partial clinical hold as quickly as possible," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "Over 500 patients have been treated with azenosertib monotherapy to date, and we believe that our data indicate a favorable therapeutic index that could potentially offer meaningful benefits to women facing PROC and USC. We have completed enrollment for Cohort 1b of the DENALI study, where we’ve enrolled more than a hundred patients, further demonstrating the support we’ve seen for having a novel oral therapy like azenosertib. We look forward to sharing these results along with overall efficacy and safety data from DENALI Cohort 1b later this year."

In addition to sharing topline results of Cohort 1b of DENALI, the Company remains on track to present results from the ZN-c3-001 and Phase 1/2 ZN-c3-006 (MAMMOTH) studies later this year. The Company will provide additional updates to the azenosertib clinical development and other data timelines following resolution of the partial clinical hold. Zentalis remains committed to the azenosertib development program and bringing this potentially practice-changing therapy to patients with gynecological malignancies.

Conference Call Details
Zentalis will host a live conference call and webcast today at 8:00 a.m. Eastern Time to provide a business update. To access the live conference call by telephone, please register at: https://register.vevent.com/register/BI24249bb9e5714044b9f4057f28565923. Upon registering, each participant will be provided with call details and access codes. The live webcast may be accessed by visiting the event link at: View Source The webcast will also be made available on the Company’s website at www.zentalis.com under the Investors & Media section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On June 18, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported randomization of the first patient in the PRISM-MEL-301 trial, assessing the efficacy and safety of brenetafusp (IMC-F106C; PRAME-A02), in combination with nivolumab, in first-line advanced or metastatic cutaneous melanoma (Press release, Immunocore, JUN 18, 2024, View Source [SID1234644424]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very proud to have started the registrational program for brenetafusp, our PRAME candidate, supported by the recent promising brenetafusp monotherapy data in late-line cutaneous melanoma" said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The PRISM-MEL-301 trial – the first Phase 3 trial for any PRAME-targeted therapy – will test whether combining brenetafusp with nivolumab may be a more effective treatment option than current standards of care for newly diagnosed metastatic or advanced cutaneous melanoma patients."

The Phase 3 trial (NCT06112314) will randomize HLA-A*02:01 positive patients with first-line, advanced or metastatic cutaneous melanoma to brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country. Bristol Myers Squibb will provide nivolumab.

Professor Georgina Long, Co-Medical Director of Melanoma Institute Australia, said: "The PRISM-MEL-301 Phase 3 trial is a great example of outside-the-box scientific thinking, leveraging the immune system in a new way in the hope of beating cancer. My hope is that we can get closer to our goal of zero deaths from melanoma by conducting clinical trials with innovative drug therapies such as this."

The Company has shared the cutaneous melanoma Phase 1 data during an oral presentation at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on 31 May. The data showed that brenetafusp was well tolerated as monotherapy and in combination with anti-PD1, and demonstrated promising monotherapy clinical activity, including disease control rate (partial response and stable disease), progression free survival, and circulating tumor DNA molecular response.

Brenetafusp is the first PRAME x CD3 ImmTAC bispecific protein targeting an HLA-A*02:01 PRAME (PReferentially expressed Antigen in Melanoma) antigen. The Company is continuing to enroll patients into a Phase 1/2 trial in monotherapy and combination arms across multiple tumor types, including three expansion arms for patients with advanced ovarian, non-small cell lung, and endometrial cancers.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About PRISM-MEL-301 – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial will randomize HLA-A*02:01-positive patients with previously untreated advanced melanoma to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and control arm and will discontinue one of the brenetafusp dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company has initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, NSCLC, and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Ph1 monotherapy continues in additional solid tumors as well as multiple combinations with standards-of-care, including checkpoint inhibitors, chemotherapy, targeted therapies, and tebentafusp.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.

On June 18, 2024 Ability Biologics ("Ability") reported the final closing of its seed funding, raising a total of $18 million (US), a financing round led by founding investor Amplitude Ventures ("Amplitude") (Press release, Ability Biotherapeutics, JUN 18, 2024, View Source [SID1234653581]). Amplitude is joined by the Fonds de solidarité FTQ, Investissement Québec, Charles River Laboratories, Theodorus and Alexandria Venture Investments. Ability, a pioneer in the application of generative Artificial Intelligence (AI) to therapeutic discovery, focuses its platform on discovering and developing potent and selective antibody therapeutics for cancer and immune-related disorders. Ability Biologics, through its AbiLeap discovery engine, is generating novel, logic-enabled antibodies with the potential to become best-in-class or first-in-class therapeutics.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Ability’s leadership team combines deep experience in immunology, antibody discovery, engineering and therapeutic development, from the bench to commercial stage, and is leveraging this experience to create next generation antibodies using powerful computational tools through its unique, proprietary AI platform. The AbiLeap discovery engine is an AI platform built on top of one of the largest databases of antibody-antigen interactions ever constructed, bringing together more than five years of discovery data and incorporating both public and private data sources. AbiLeap allows Ability to address a longstanding challenge by generating fully human antibodies that are logic-gated, enabling them to target specific tissues and cells based on the local microenvironment, including conditions such as secondary antigens, pH, temperature and/or the presence of specific metabolites.

"We’re seeing a need for a new generation of antibodies and modalities as simply binding, blocking or agonizing a single receptor is not enough to achieve therapeutic impact," said Giles Day, Co-founder and CEO of Ability. "At Ability, our platform overlays multiple approaches in a single molecule, enhancing specificity and selectivity to develop potent therapeutics with broad therapeutic windows. To do so, our antibodies employ tried and tested IgG formats that enable easier manufacturing, storage and administration, avoiding complex formats that introduce multiple risks from manufacturing to immunogenicity," concluded Giles Day.

"We are focused on solving the next set of complex biology challenges and one of them is to tackle the issue of on-target, off-tissue toxicity, which is limiting the utility of antibody therapy," said Dion Madsen, CFA, Co-founder and Partner at Amplitude Ventures. "Ability’s proprietary platform stands out as an intelligent way of rapidly developing selective and potent, ultra-targeted biotherapeutics to enhance potency and patient outcomes."

"The life science and biotech sector is in constant flux, and we are proud to provide financial backing for Ability’s ongoing innovations," said Bicha Ngo, President and CEO of Investissement Québec. "Harnessing the latest technologies, like artificial intelligence, in the development of antibodies will solidify Québec’s expertise in an area that is critical to the treatment of various types of cancer, and ultimately other diseases, that affect many Quebecers every year."